R. H. Abhold, M. J. Sullivan, J. W. Wright, and J. W. Harding, Binding, degradation and pressor activity of angiotensins II and III after aminopeptidase inhibition with amastatin and bestatin, J. Pharmacol. Exp. Ther, vol.242, pp.957-962, 1987.

&. , .. J. , &. , .. D. Àferario, and C. M. , Angiotensin-(1-12): a chymase-mediated cellular angiotensin II substrate, Curr. Hypertens. Rep, vol.16, p.429, 2014.

S. Ahmad and P. E. Ward, Role of aminopeptidase activity in the regulation of the pressor activity of circulating angiotensins, J. Pharmacol. Exp. Ther, vol.252, pp.643-650, 1990.

A. L. Albiston, S. G. Mcdowall, D. Matsacos, P. Sim, E. Clune et al., Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase, J. Biol. Chem, vol.276, pp.48623-48626, 2001.

A. M. Allen, S. Y. Chai, J. Clevers, M. J. Mckinley, G. Paxinos et al., Localization and characterization of angiotensin II receptor binding and angiotensin converting enzyme in the human medulla oblongata, J. Comp. Neurol, vol.269, pp.249-264, 1988.

A. M. Allen, D. P. Macgregor, S. Y. Chai, G. A. Donnan, S. Kaczmarczyk et al., Angiotensin II receptor binding associated with nigrostriatal dopaminergic neurons in human basal ganglia, Ann. Neurol, vol.32, pp.339-344, 1992.

A. M. Allen, J. Zhuo, and F. A. Mendelsohn, Localization and function of angiotensin AT1 receptors, Am. J. Hypertens, vol.13, pp.31-38, 2000.

F. Alliot, J. Rutin, P. J. Leenen, and B. Pessac, Brain parenchyma vessels and the angiotensin system, Brain Res, vol.830, pp.101-112, 1999.

F. Alliot, J. Rutin, P. J. Leenen, and B. Pessac, Pericytes and periendothelial cells of brain parenchyma vessels co-express aminopeptidase N, aminopeptidase A, and nestin, J. Neurosci. Res, vol.58, pp.367-378, 1999.

T. Aoyagi, M. Nagai, M. Iwabuchi, W. S. Liaw, T. Andoh et al., Aminopeptidase activities on the surface of mammalian cells and their alterations associated with transformation, Cancer Res, vol.38, pp.3505-3508, 1978.

T. Aoyagi, H. Tobe, F. Kojima, M. Hamada, T. Takeuchi et al., Amastatin, an inhibitor of aminopeptidase A, produced by actinomycetes, J. Antibiot, vol.31, pp.636-638, 1978.

T. Aoyagi, T. Wada, F. Kojima, M. Nagai, S. Harada et al., Inhibitors of aminopeptidase B suppress the development of hypertension in 156 spontaneously hypertensive rats, Chem. Pharm. Bull, vol.34, pp.4852-4854, 1986.

T. Aoyagi, S. Yoshida, Y. Nakamura, Y. Shigihara, M. Hamada et al., Probestin, a new inhibitor of aminopeptidase M, produced by Streptomyces azureus MH663-2F6. I, 1990.

, Taxonomy, production, isolation, physico-chemical properties and biological activities, J. Antibiot, vol.43, pp.143-148

E. Archer-lahlou, I. Tikhonova, C. Escrieut, M. Dufresne, C. Seva et al., Modeled structure of a G-protein-coupled receptor: the cholecystokinin-1 receptor, J. Med. Chem, vol.48, pp.180-191, 2005.

A. C. Arnold, K. Isa, H. A. Shaltout, M. Nautiyal, C. M. Ferrario et al., Angiotensin-(1-12) requires angiotensin converting enzyme and AT1 receptors for cardiovascular actions within the solitary tract nucleus, Am. J. Physiol. Heart Circ. Physiol, vol.299, pp.763-771, 2010.

E. A. Ashley, J. Powers, M. Chen, R. Kundu, T. Finsterbach et al., The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo, Cardiovasc. Res, vol.65, pp.73-82, 2005.

K. J. Assmann, J. P. Van-son, H. B. Dijkman, and R. A. Koene, A nephritogenic rat monoclonal antibody to mouse aminopeptidase A. Induction of massive albuminuria after a single intravenous injection, J. Exp. Med, vol.175, pp.623-635, 1992.

M. Azizi, X. Iturrioz, A. Blanchard, S. Peyrard, N. De-mota et al., Reciprocal regulation of plasma apelin and vasopressin by osmotic stimuli.-PubMed-NCBI, Journal of American Society of Nephrology, 2008.
URL : https://hal.archives-ouvertes.fr/inserm-00422689

M. Azzi, P. G. Charest, S. Angers, G. Rousseau, T. Kohout et al., Beta-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors, Proc. Natl. Acad. Sci. U.S.A, vol.100, pp.11406-11411, 2003.

B. Bai, L. Liu, N. Zhang, C. Wang, Y. Jiang et al., Heterodimerization of human apelin and bradykinin 1 receptors: novel signal transduction characteristics, Cell. Signal, vol.26, pp.1549-1559, 2014.

B. Bai, J. Tang, H. Liu, J. Chen, Y. Li et al., Apelin-13 induces ERK1/2 but not p38 MAPK activation through coupling of the human apelin receptor to the Gi2 pathway, Acta Biochim. Biophys. Sin. (Shanghai), vol.40, pp.311-318, 2008.

J. G. Baker, I. P. Hall, and S. J. Hill, Agonist and inverse agonist actions of beta-blockers at the human beta 2-adrenoceptor provide evidence for agonist-directed signaling, Mol. Pharmacol, vol.64, pp.1357-1369, 2003.

S. Balanescu, P. Kopp, M. B. Gaskill, N. G. Morgenthaler, C. Schindler et al., Correlation of plasma copeptin and vasopressin concentrations in hypo-, iso-, and 157 hyperosmolar States, J. Clin. Endocrinol. Metab, vol.96, pp.1046-1052, 2011.

F. Balavoine, M. Azizi, D. Bergerot, N. De-mota, R. Patouret et al., Randomised, double-blind, placebo-controlled, dose-escalating phase I study of QGC001, a centrally acting aminopeptidase a inhibitor prodrug, Clin Pharmacokinet, vol.53, pp.385-395, 2014.

J. .. Ballesteros and H. Weinstein, Integrated methods for the construction of threedimensional models and computational probing of structure-function relations in G proteincoupled receptors, Receptor Molecular Biology, Methods in Neurosciences, pp.366-428, 1995.

M. Bally, M. Murgier, and A. Lazdunski, Cloning and orientation of the gene encoding aminopeptidase N in Escherichia coli, Mol. Gen. Genet, vol.195, pp.507-510, 1984.

A. Balogh, S. Cadel, T. Foulon, R. Picart, A. Der-garabedian et al., Aminopeptidase B: a processing enzyme secreted and associated with the plasma membrane of rat pheochromocytoma (PC12) cells, J. Cell. Sci, vol.111, pp.161-169, 1998.

G. D. Barnes, S. Alam, G. Carter, C. M. Pedersen, K. M. Lee et al., Sustained cardiovascular actions of APJ agonism during renin-angiotensin system activation and in patients with heart failure, Circ Heart Fail, vol.6, pp.482-491, 2013.

P. A. Bartlett and C. K. Marlowe, Possible role for water dissociation in the slow binding of phosphorus-containing transition-state-analogue inhibitors of thermolysin, Biochemistry, vol.26, pp.8553-8561, 1987.

N. Basso, P. Ruiz, E. Mangiarua, and A. C. Taquini, Renin-like activity in the rat brain during the development of DOC-salt hypertension, Hypertension, vol.3, pp.14-17, 1981.

J. M. Bathon, D. Proud, S. Mizutani, and P. E. Ward, Cultured human synovial fibroblasts rapidly metabolize kinins and neuropeptides, J. Clin. Invest, vol.90, pp.981-991, 1992.

C. M. Batt, E. W. Klein, J. W. Harding, and J. W. Wright, Pressor responses to amastatin, estatià aadà Pluuueeesà ihiitoosà aaeà supppessedà à ppetteatteetà ithà theà aagioteesià receptor antagonist sarthran, Brain Res. Bull, vol.21, pp.731-735, 1988.

U. Baumann, Crystal structure of the 50 kDa metallo protease from Serratia marcescens, J. Mol. Biol, vol.242, pp.244-251, 1994.

H. H. Bausback, L. Churchill, and P. E. Ward, Angiotensin metabolism by cerebral microvascular aminopeptidase A, Biochem. Pharmacol, vol.37, pp.155-160, 1988.

H. H. Bausback and P. E. Ward, Degradation of low-molecular-weight opioid peptides by vascular plasma membrane aminopeptidase M, Biochim. Biophys. Acta, vol.882, pp.437-444, 1986.

À. Beauuoot, .. J. Àfouuuizaluski, M. C. Roques, and B. P. , The role of histidine 231 in thermolysin-like enzymes. A sitedirected mutagenesis study, J. Biol. Chem, vol.270, pp.16803-16808, 1995.

N. Belhacene, B. Mari, B. Rossi, and P. Auberger, Characterization and purification of T lymphocyte aminopeptidase B: a putative marker of T cell activation, Eur. J. Immunol, vol.23, pp.1948-1955, 1993.

A. Benajiba and S. Maroux, Purification and characterization of an aminopeptidase A from hog intestinal brush-border membrane, Eur. J. Biochem, vol.107, pp.381-388, 1980.

J. L. Benovic, H. Kühn, I. Weyand, J. Codina, M. G. Caron et al., Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein), Proc. Natl. Acad. Sci. U.S.A, vol.84, pp.8879-8882, 1987.

J. L. Benovic, L. J. Pike, R. A. Cerione, C. Staniszewski, T. Yoshimasa et al., Phosphorylation of the mammalian beta-adrenergic receptor by cyclic AMP-dependent protein kinase. Regulation of the rate of receptor phosphorylation and dephosphorylation by agonist occupancy and effects on coupling of the receptor to the stimulatory guanine nucleotide regulatory protein, J. Biol. Chem, vol.260, pp.7094-7101, 1985.

M. F. Berry, T. J. Pirolli, V. Jayasankar, J. Burdick, K. J. Morine et al., Apelin has in vivo inotropic effects on normal and failing hearts, Circulation, vol.110, pp.187-193, 2004.
DOI : 10.1161/01.cir.0000138382.57325.5c

URL : https://www.ahajournals.org/doi/pdf/10.1161/01.CIR.0000138382.57325.5c

D. M. Bers, Cardiac excitation-contraction coupling, Nature, vol.415, pp.198-205, 2002.

S. V. Bhagwat, J. Lahdenranta, R. Giordano, W. Arap, R. Pasqualini et al., , 2001.

, APN is activated by angiogenic signals and is essential for capillary tube formation, Blood, vol.97, pp.652-659

F. Binkley, V. Alexander, F. E. Bell, and C. Lea, Peptidases and alkaline phosphatases of swine kidney, J. Biol. Chem, vol.228, pp.559-567, 1957.

A. Blanchard, O. Steichen, N. De-mota, E. Curis, C. Gauci et al., An abnormal apelin/vasopressin balance may contribute to water retention in patients with the syndrome of inappropriate antidiuretic hormone (SIADH) and heart failure, J. Clin. Endocrinol. Metab, vol.98, pp.2084-2089, 2013.

T. L. Blundell, Metalloproteinase superfamilies and drug design, Nat. Struct. Biol, vol.1, pp.73-75, 1994.

W. Bode, F. X. Gomis-rüth, and W. Stöckler, Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Mettuuuuàaadàtopologiesàaadàshouldàeàggoupedàitoàaàoooooàfaail,àtheàetziis, FEBS Lett, vol.331, pp.134-140, 1993.

L. Bodineau, A. Hus-citharel, and C. Llorens-cortes, , 2010.

, Ann. Endocrinol. (Paris), vol.71, pp.249-256

L. Bodineau, C. Taveau, H. Lê-quan-sang, G. Osterstock, I. Queguiner et al., Data supporting a new physiological role for brain apelin in the regulation of hypothalamic oxytocin neurons in lactating rats, Endocrinology, vol.152, pp.3492-3503, 2011.

À. X. Bogdaaooi?, G. J. Hheeteit, J. Singh, R. K. Gudmundsdóttir, B. K. Hinrichs et al., Structural evidence of intramolecular propeptide inhibition of the aspzincin metalloendopeptidase AsaP1, FEBS Lett, vol.590, pp.3280-3294, 2016.

T. Bogenrieder, C. L. Finstad, R. H. Freeman, C. N. Papandreou, H. I. Scher et al., Expression and localization of aminopeptidase A, aminopeptidase N, and dipeptidyl peptidase IV in benign and malignant human prostate tissue, Prostate, vol.33, pp.225-232, 1997.

F. Bornancin, C. Pfister, and M. Chabre, The transitory complex between photoexcited rhodopsin and transducin. Reciprocal interaction between the retinal site in rhodopsin and the nucleotide site in transducin, Eur. J. Biochem, vol.184, pp.687-698, 1989.

J. Boucher, B. Masri, D. Daviaud, S. Gesta, C. Guigné et al., Apelin, a newly identified adipokine up-regulated by insulin and obesity, Endocrinology, vol.146, pp.1764-1771, 2005.
URL : https://hal.archives-ouvertes.fr/inserm-00480981

J. Bouhnik, E. Clauser, D. Strosberg, J. P. Frenoy, J. Menard et al., Rat angiotensinogen and des(angiotensin I)angiotensinogen: purification, characterization, and partial sequencing, Biochemistry, vol.20, pp.7010-7015, 1981.
DOI : 10.1021/bi00527a036

A. Bourne, K. Barnes, B. A. Taylor, A. J. Turner, and A. J. Kenny, Membrane peptidases in the pig choroid plexus and on other cell surfaces in contact with the cerebrospinal fluid, Biochem. J, vol.259, pp.69-80, 1989.

M. Bouvier, .. P. Hausdoff, .. F. , .. K. , .. G. et al., Removal of phosphorylation sites from the beta 2-adrenergic receptor delays onset of agonist-promoted desensitization, Nature, vol.333, pp.370-373, 1988.

M. Bouvier, L. M. Leeb-lundberg, J. L. Benovic, M. G. Caron, and R. J. Lefkowitz, Regulation of adrenergic receptor function by phosphorylation. II. Effects of agonist occupancy on phosphorylation of alpha 1-and beta 2-adrenergic receptors by protein kinase C and the cyclic AMP-dependent protein kinase, J. Biol. Chem, vol.262, pp.3106-3113, 1987.

G. C. Brailoiu, S. L. Dun, J. Yang, M. Ohsawa, J. K. Chang et al., Apelinimmunoreactivity in the rat hypothalamus and pituitary, Neurosci. Lett, vol.327, pp.193-197, 2002.

A. L. Brame, J. J. Maguire, P. Yang, A. Dyson, R. Torella et al., Design, characterization, and first-in-human study of the vascular actions of a novel biased apelin receptor agonist, Hypertension, vol.65, pp.834-840, 2015.

C. K. Brown, K. Madauss, W. Lian, M. R. Beck, W. D. Tolbert et al., Structure of neurolysin reveals a deep channel that limits substrate access, Proc. Natl. Acad. Sci. U.S.A, vol.98, pp.3127-3132, 2001.

J. H. Brown and D. Goldstein, Differences in muscarinic receptor reserve for inhibition of adenylate cyclase and stimulation of phosphoinositide hydrolysis in chick heart cells, Mol. Pharmacol, vol.30, pp.566-570, 1986.

M. J. Brownstein, J. T. Russell, and H. Gainer, Synthesis, transport, and release of posterior pituitary hormones, Science, vol.207, pp.373-378, 1980.

J. Buggy, G. D. Fink, A. K. Johnson, and M. J. Brody, Prevention of the development of renal hypertension by anteroventral third ventricular tissue lesions, Circ. Res, vol.40, pp.110-117, 1977.

B. Bunnemann, K. Fuxe, R. Metzger, B. Bjelke, and D. Ganten, The semi-quantitative distribution and cellular localization of angiotensinogen mRNA in the rat brain, J. Chem. Neuroanat, vol.5, pp.245-262, 1992.

R. M. Burch, A. Luini, and J. Axelrod, Phospholipase A2 and phospholipase C are activated by distinct GTP-binding proteins in response to alpha 1-adrenergic stimulation in FRTL5 thyroid cells, Proc. Natl. Acad. Sci. U.S.A, vol.83, pp.7201-7205, 1986.

S. Cadel, C. Darmon, J. Pernier, G. Hervé, and T. Foulon, The M1 family of vertebrate aminopeptidases: role of evolutionarily conserved tyrosines in the enzymatic mechanism of aminopeptidase B, Biochimie, vol.109, pp.67-77, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01558872

S. Cadel, T. Foulon, A. Viron, A. Balogh, S. Midol-monnet et al., Aminopeptidase B from the rat testis is a bifunctional enzyme structurally related to leukotriene-A4 hydrolase, Proc. Natl. Acad. Sci. U.S.A, vol.94, pp.2963-2968, 1997.

S. Cadel, A. R. Pierotti, T. Foulon, C. Créminon, N. Barré et al., Aminopeptidase-B in the rat testes: isolation, functional properties and cellular localization in the seminiferous tubules, Mol. Cell. Endocrinol, vol.110, pp.149-160, 1995.

T. J. Cahill, A. R. Thomsen, J. T. Tarrasch, B. Plouffe, A. H. Nguyen et al., Distinct conformations of GPCR-?-arrestin complexes mediate desensitization, signaling, and endocytosis, Proc. Natl. Acad. Sci. U.S.A, vol.114, pp.2562-2567, 2017.

X. Cai, B. Bai, R. Zhang, C. Wang, and J. Chen, Apelin receptor homodimer-oligomers revealed by single-molecule imaging and novel G protein-dependent signaling, Sci Rep, vol.7, p.40335, 2017.

I. Castan-laurell, C. Dray, C. Attané, T. Duparc, C. Knauf et al., Apelin, diabetes, and obesity, Endocrine, vol.40, pp.1-9, 2011.
DOI : 10.1007/s12020-011-9507-9

URL : https://hal.archives-ouvertes.fr/inserm-00617638

M. G. Castro, N. P. Birch, and Y. P. Loh, Regulated secretion of pro-opiomelanocortin converting enzyme and an aminopeptidase B-like enzyme from dispersed bovine intermediate lobe pituitary cells, J. Neurochem, vol.52, pp.1619-1628, 1989.

J. Célérier, A. Cruz, N. Lamandé, J. Gasc, and P. Corvol, Angiotensinogen and its cleaved derivatives inhibit angiogenesis, Hypertension, vol.39, pp.224-228, 2002.

E. Ceraudo, C. Galanth, E. Carpentier, I. Banegas-font, A. Schonegge et al., Biased signaling favoring gi over ?-arrestin promoted by an apelin fragment lacking the C-terminal phenylalanine, J. Biol. Chem, vol.289, pp.24599-24610, 2014.

S. Y. Chai, J. Zhuo, and F. A. Mendelsohn, Localization of components of the reninangiotensin system and site of action of inhibitors, Arzneimittelforschung, vol.43, pp.214-221, 1993.

D. Chansel, S. Czekalski, S. Vandermeersch, E. Ruffet, M. C. Fournié-zaluski et al., Characterization of angiotensin IV-degrading enzymes and receptors on rat mesangial cells, Am. J. Physiol, vol.275, pp.535-542, 1998.

E. N. Chauvel, P. Coric, C. Llorens-cortès, S. Wilk, B. P. Roques et al., Investigation of the active site of aminopeptidase A using a series of new thiol-containing inhibitors, J. Med. Chem, vol.37, pp.1339-1346, 1994.

E. N. Chauvel, C. Llorens-cortès, P. Coric, S. Wilk, B. P. Roques et al., Differential inhibition of aminopeptidase A and aminopeptidase N by new beta-amino thiols, J. Med. Chem, vol.37, pp.2950-2957, 1994.

L. Chen, Y. Lin, G. Peng, and F. Li, Structural basis for multifunctional roles of mammalian aminopeptidase N, Proc. Natl. Acad. Sci. U.S.A, vol.109, pp.17966-17971, 2012.

M. M. Chen, E. A. Ashley, D. X. Deng, A. Tsalenko, A. Deng et al., Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction, Circulation, vol.108, pp.1432-1439, 2003.

W. J. Chen, J. L. Goldstein, and M. S. Brown, NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor, J. Biol. Chem, vol.265, pp.3116-3123, 1990.

X. Chen, B. Bai, Y. Tian, H. Du, and J. Chen, Identification of serine 348 on the apelin receptor as a novel regulatory phosphorylation site in apelin-13-induced G proteinindependent biased signaling, J. Biol. Chem, vol.289, pp.31173-31187, 2014.

X. Cheng, X. S. Cheng, and C. C. Pang, Venous dilator effect of apelin, an endogenous peptide ligand for the orphan APJ receptor, in conscious rats, Eur. J. Pharmacol, vol.470, pp.171-175, 2003.

M. H. Chin and L. Goldman, Correlates of major complications or death in patients admitted to the hospital with congestive heart failure, Arch. Intern. Med, vol.156, pp.1814-1820, 1996.

V. C. Chitravanshi, A. Proddutur, and H. N. Sapru, Cardiovascular actions of angiotensin-(112) in the hypothalamic paraventricular nucleus of the rat are mediated via angiotensin II, Exp. Physiol, vol.97, pp.1001-1017, 2012.

V. C. Chitravanshi and H. N. Sapru, Cardiovascular responses elicited by a new endogenous angiotensin in the nucleus tractus solitarius of the rat, Am. J. Physiol. Heart Circ. Physiol, vol.300, pp.230-240, 2011.

W. Choe, A. Albright, J. Sulcove, S. Jaffer, J. Hesselgesser et al., Functional expression of the seven-transmembrane HIV-1 co-receptor APJ in neural cells, J. Neurovirol, vol.6, pp.61-69, 2000.

K. S. Chong, R. S. Gardner, J. J. Morton, E. A. Ashley, and T. A. Mcdonagh, Plasma concentrations of the novel peptide apelin are decreased in patients with chronic heart failure, Eur. J. Heart Fail, vol.8, pp.355-360, 2006.

M. Christ-crain and W. Fenske, Copeptin in the diagnosis of vasopressin-dependent disorders of fluid homeostasis, Nat Rev Endocrinol, vol.12, pp.168-176, 2016.

D. W. Christianson and R. S. Alexander, Another catalytic triad?, Nature, vol.346, p.225, 1990.

A. Christopoulos and T. Kenakin, G protein-coupled receptor allosterism and complexing, Pharmacol. Rev, vol.54, pp.323-374, 2002.

H. J. Chun, Z. A. Ali, Y. Kojima, R. K. Kundu, A. Y. Sheikh et al., Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis, J. Clin. Invest, vol.118, pp.3343-3354, 2008.

A. Chung, J. W. Ryan, and P. Berryer, Inhibition of the formation of angiotensin III, Adv. Exp. Med. Biol, vol.156, pp.693-701, 1983.

L. Churchill, H. H. Bausback, M. E. Gerritsen, and P. E. Ward, Metabolism of opioid peptides by cerebral microvascular aminopeptidase M, Biochim. Biophys. Acta, vol.923, pp.35-41, 1987.

M. Cirilli, C. Gallina, E. Gavuzzo, C. Giordano, F. X. Gomis-rüth et al., angstrom X-ray structure of adamalysin II complexed with a peptide phosphonate inhibitor adopting a retro-binding mode, FEBS Lett, vol.2, pp.319-322, 1997.

C. Claperon, I. Banegas-font, X. Iturrioz, R. Rozenfeld, B. Maigret et al., Identification of threonine 348 as a residue involved in aminopeptidase A substrate specificity, p.163, 2009.
URL : https://hal.archives-ouvertes.fr/inserm-00418798

, J. Biol. Chem, vol.284, pp.10618-10626

C. Claperon, R. Rozenfeld, X. Iturrioz, N. Inguimbert, M. Okada et al., Asp218 participates with Asp213 to bind a Ca2+ atom into the S1 subsite of aminopeptidase A: a key element for substrate specificity, Biochem. J, vol.416, pp.37-46, 2008.
URL : https://hal.archives-ouvertes.fr/hal-00478991

S. Cockcroft and B. D. Gomperts, Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase, Nature, vol.314, pp.534-536, 1985.

P. Cohen, Proteolytic events in the post-translational processing of polypeptide hormone precursors, Biochimie, vol.69, pp.87-89, 1987.

D. E. Coleman, A. M. Berghuis, E. Lee, M. E. Linder, A. G. Gilman et al., Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis, Science, vol.265, pp.1405-1412, 1994.

P. M. Colman, J. N. Jansonius, and B. W. Matthews, The structure of thermolysin: an electron density map at 2-3 A resolution, J. Mol. Biol, vol.70, pp.701-724, 1972.

M. Congreve, C. J. Langmead, J. S. Mason, and F. H. Marshall, Progress in structure based drug design for G protein-coupled receptors, J. Med. Chem, vol.54, pp.4283-4311, 2011.

V. I. Cook, J. W. Wright, S. A. Wright, and J. W. Harding, Comparison of angiotensin metabolism by brain membranes from SHR and WKY rats, Brain Res, vol.529, pp.320-323, 1990.

M. D. Cooper, D. Mulvaney, A. Coutinho, and P. A. Cazenave, A novel cell surface molecule on early B-lineage cells, Nature, vol.321, pp.616-618, 1986.

C. M. Costa-neto, -. Parreiras, L. T. Silva, and M. Bouvier, A Pluridimensional View of Biased Agonism, Mol. Pharmacol, vol.90, pp.587-595, 2016.

L. Dai, P. M. Smith, M. Kuksis, and A. V. Ferguson, Apelin acts in the subfornical organ to influence neuronal excitability and cardiovascular function, J. Physiol. (Lond.), vol.591, pp.3421-3432, 2013.

T. Dai, G. Ramirez-correa, and W. D. Gao, Apelin increases contractility in failing cardiac muscle, Eur. J. Pharmacol, vol.553, pp.222-228, 2006.

S. Dalal, D. R. Ragheb, F. D. Schubot, and M. Klemba, A naturally variable residue in the S1 subsite of M1 family aminopeptidases modulates catalytic properties and promotes functional specialization, J. Biol. Chem, vol.288, pp.26004-26012, 2013.

À. Ddááiello, &. , .. M. , .. L. Carmeliet, P. Minchiotti et al., G protein-coupled receptor APJ and its ligand apelin act downstream of Cripto to specify embryonic stem cells toward the cardiac lineage through extracellular signal-regulated kinase/p70S6 kinase signaling pathway, Circ. Res, vol.105, pp.231-238, 2009.

E. M. Danielsen, O. Norén, H. Sjöström, J. Ingram, and A. J. Kenny, Proteins of the kidney microvillar membrane. Aspartate aminopeptidase: purification by immunoadsorbent chromatography and properties of the detergent-and proteinase-solubilized forms, Biochem. J, vol.189, pp.591-603, 1980.

C. David, L. Bischoff, H. Meudal, C. Llorens-cortes, B. P. Roques et al., Characterization and inhibition of aminopeptidase A by ?-mercapto-?-amino acyl dipeptides, Letters in Peptide Science, vol.4, pp.411-414, 1997.
URL : https://hal.archives-ouvertes.fr/hal-02122127

C. David, L. Bischoff, H. Meudal, A. Mothé, N. De-mota et al., 7) led to the design of the first highly potent and selective inhibitors of this enzyme, J. Med. Chem, vol.42, pp.5197-5211, 1999.
URL : https://hal.archives-ouvertes.fr/hal-02122148

M. De-falco, L. De-luca, N. Onori, I. Cavallotti, F. Artigiano et al., Apelin expression in normal human tissues, In Vivo, vol.16, pp.333-336, 2002.

C. De-graaf, S. Nijmeijer, S. Wolf, and O. P. Ernst, 7TM Domain Structure of Adhesion GPCRs, Handb Exp Pharmacol, vol.234, pp.43-66, 2016.

N. De-mota, X. Iturrioz, C. Claperon, L. Bodineau, C. Fassot et al., Human brain aminopeptidase A: biochemical properties and distribution in brain nuclei, J. Neurochem, vol.106, pp.416-428, 2008.
URL : https://hal.archives-ouvertes.fr/inserm-00422677

N. De-mota, Z. Lenkei, and C. Llorens-cortès, Cloning, pharmacological characterization and brain distribution of the rat apelin receptor, Neuroendocrinology, vol.72, pp.400-407, 2000.

N. De-mota, . Reaux-le, A. Goazigo, S. El-messari, N. Chartrel et al., Apelin, a potent diuretic neuropeptide counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release, 2004.

M. Y. Degtyarev, A. M. Spiegel, and T. L. Jones, Palmitoylation of a G protein alpha i subunit requires membrane localization not myristoylation, J. Biol. Chem, vol.269, pp.30898-30903, 1994.

D. Vecchio, P. J. Ryan, J. W. Chung, A. Ryan, and U. S. , Capillaries of the adrenal cortex possess aminopeptidase A and angiotensin-converting-enzyme activities, Biochem. J, vol.186, pp.605-608, 1980.

C. F. Deschepper, J. Bouhnik, and W. F. Ganong, Colocalization of angiotensinogen and glial fibrillary acidic protein in astrocytes in rat brain, Brain Res, vol.374, pp.195-198, 1986.

A. Devault, C. Lazure, C. Nault, H. Le-moual, N. G. Seidah et al., Amino acid sequence of rabbit kidney neutral endopeptidase 24.11 (enkephalinase) deduced from a complementary DNA, EMBO J, vol.6, pp.1317-1322, 1987.

E. Devic, L. Paquereau, P. Vernier, B. Knibiehler, and Y. Audigier, Expression of a new G Functional dissociation of apelin receptor signaling and endocytosis: implications for the effects of apelin on arterial blood pressure, J. Neurochem, vol.90, pp.1290-1301, 1996.

D. H. Ellison and T. Berl, Clinical practice. The syndrome of inappropriate antidiuresis, N. Engl. J. Med, vol.356, pp.2064-2072, 2007.

E. G. Erdös, Angiotensin I converting enzyme, Circ. Res, vol.36, pp.247-255, 1975.

M. Eyries, G. Siegfried, M. Ciumas, K. Montagne, M. Agrapart et al., Hypoxia-induced apelin expression regulates endothelial cell proliferation and regenerative angiogenesis, Circ. Res, vol.103, pp.432-440, 2008.

C. Fahlke, D. Kortzak, and J. Machtens, Molecular physiology of EAAT anion channels, Pflugers Arch, vol.468, pp.491-502, 2016.

X. Fan, N. Zhou, X. Zhang, M. Mukhtar, Z. Lu et al., Structural and functional study of the apelin-13 peptide, an endogenous ligand of the HIV-1 coreceptor, APJ. Biochemistry, vol.42, pp.10163-10168, 2003.

K. Farkasfalvi, M. A. Stagg, S. R. Coppen, U. Siedlecka, J. Lee et al., Direct effects of apelin on cardiomyocyte contractility and electrophysiology, Biochem. Biophys. Res. Commun, vol.357, pp.889-895, 2007.

D. T. Fei, J. P. Coghlan, B. A. Scoggins, and J. J. Tresham, In vivo conversion of [des-Asp1]angiotensin I to [des-Asp1]-angiotensin II in conscious sheep, Clin Exp Pharmacol Physiol Suppl, vol.7, pp.41-44, 1982.

D. Felix and W. Schlegel, Angiotensin receptive neurones in the subfornical organ. Structure-activity relations, Brain Res, vol.149, pp.107-116, 1978.

W. Fenske, S. Störk, A. Blechschmidt, S. G. Maier, N. G. Morgenthaler et al., Copeptin in the differential diagnosis of hyponatremia, J. Clin. Endocrinol. Metab, vol.94, pp.123-129, 2009.

H. Feracci and S. Maroux, Rabbit intestinal aminopeptidase N. Purification and molecular properties, Biochim. Biophys. Acta, vol.599, pp.448-463, 1980.

A. V. Ferguson, Angiotensinergic regulation of autonomic and neuroendocrine outputs: critical roles for the subfornical organ and paraventricular nucleus, Neuroendocrinology, vol.89, pp.370-376, 2009.

S. S. Ferguson, L. S. Barak, J. Zhang, and M. G. Caron, G-protein-coupled receptor regulation: role of G-protein-coupled receptor kinases and arrestins. Can, J. Physiol. Pharmacol, vol.74, pp.1095-1110, 1996.

S. S. Ferguson, W. E. Downey, A. M. Colapietro, L. S. Barak, L. Ménard et al., Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization, Science, vol.271, pp.363-366, 1996.

, Phylogenetic analysis, paralogon groups, and fingerprints, the human genome form five main families, vol.63, pp.1256-1272

F. Frigerio, I. Margarit, R. Nogarotto, G. Grandi, G. Vriend et al., Model building of a thermolysin-like protease by mutagenesis, Protein Eng, vol.10, pp.223-230, 1997.

K. M. Fukasawa, J. Hirose, T. Hata, and Y. Ono, Aspartic acid 405 contributes to the substrate specificity of aminopeptidase B, Biochemistry, vol.45, pp.11425-11431, 2006.

H. Gainer, J. T. Russell, and Y. P. Loh, An aminopeptidase activity in bovine pituitary secretory vesicles that cleaves the N-terminal arginine from beta-lipotropin60-65, FEBS Lett, vol.175, pp.135-139, 1984.

C. Galanth, A. Hus-citharel, B. Li, and C. Llorens-cortès, Apelin in the control of body fluid homeostasis and cardiovascular functions, Curr. Pharm. Des, vol.18, pp.789-798, 2012.

C. Galés, J. J. Van-durm, S. Schaak, S. Pontier, Y. Percherancier et al., Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes, Nat. Struct. Mol. Biol, vol.13, pp.778-786, 2006.

H. Galon-tilleman, H. Yang, M. A. Bednarek, S. M. Spurlock, K. J. Paavola et al., Apelin36 Modulates Blood Glucose and Body Weight Independently of Canonical APJ Receptor Signaling, J. Biol. Chem, vol.292, pp.1925-1933, 2017.

D. Ganten, K. Hermann, C. Bayer, T. Unger, and R. E. Lang, Angiotensin synthesis in the brain and increased turnover in hypertensive rats, Science, vol.221, pp.869-871, 1983.

D. Ganten, J. S. Hutchinson, P. Schelling, U. Ganten, and H. Fischer, The iso-renin angiotensin systems in extrarenal tissue, Clin. Exp. Pharmacol. Physiol, vol.3, pp.103-126, 1976.

J. Gao, Y. Marc, X. Iturrioz, V. Leroux, F. Balavoine et al., A new strategy for treating hypertension by blocking the activity of the brain renin-angiotensin system with aminopeptidase A inhibitors, Clin. Sci, vol.127, pp.135-148, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02153715

P. Garrido-gil, A. I. Rodriguez-perez, P. Fernandez-rodriguez, J. L. Lanciego, and J. L. Labandeiragarcia, Expression of angiotensinogen and receptors for angiotensin and prorenin in the rat and monkey striatal neurons and glial cells, Brain Struct Funct, 2017.

P. Garrido-gil, R. Valenzuela, B. Villar-cheda, J. L. Lanciego, and J. L. Labandeira-garcia, Expression of angiotensinogen and receptors for angiotensin and prorenin in the monkey and human substantia nigra: an intracellular renin-angiotensin system in the nigra, Brain Struct Funct, vol.218, pp.373-388, 2013.

F. Gbahou, A. Rouleau, S. Morisset, R. Parmentier, S. Crochet et al., Protean agonism at histamine H3 receptors in vitro and in vivo, Proc. Natl. Acad. Sci. U.S.A, vol.100, pp.11086-11091, 2003.
URL : https://hal.archives-ouvertes.fr/hal-02081588

S. G. George and A. J. Kenny, Studies on the enzymology of purified preparations of brush border from rabbit kidney, Biochem J, vol.134, pp.43-57, 1973.

D. Georgiadis, G. Vazeux, C. Llorens-cortes, A. Yiotakis, and V. Dive, Potent and selective inhibition of zinc aminopeptidase A (EC, APA) by glutamyl aminophosphinic peptides: importance of glutamyl aminophosphinic residue in the P1 position, Biochemistry, vol.39, pp.1152-1155, 2000.

R. Gerbier, R. Alvear-perez, J. Margathe, A. Flahault, P. Couvineau et al., Development of original metabolically stable apelin-17 analogs with diuretic and cardiovascular effects, FASEB J, vol.31, pp.687-700, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02153694

R. Gerbier, V. Leroux, P. Couvineau, R. Alvear-perez, B. Maigret et al., New structural insights into the apelin receptor: identification of key residues for apelin binding, FASEB J, vol.29, pp.314-322, 2015.
URL : https://hal.archives-ouvertes.fr/hal-02153705

G. Gimpl and F. Fahrenholz, The oxytocin receptor system: structure, function, and regulation, Physiol. Rev, vol.81, pp.629-683, 2001.

G. G. Glenner and J. E. Folk, Glutamyl peptidases in rat and guinea pig kidney slices, Nature, vol.192, pp.338-340, 1961.

G. G. Glenner, P. J. Mcmillan, and J. E. Folk, A mammalian peptidase specific for the hydrolysis of N-terminal alpha-L-glutamyl and aspartyl residues, Nature, vol.194, p.867, 1962.

S. R. Goldsmith, G. S. Francis, and A. W. Cowley, Arginine vasopressin and the renal response to water loading in congestive heart failure, Am. J. Cardiol, vol.58, pp.295-299, 1986.

F. X. Gomis-rüth, W. Stöcker, R. Huber, R. Zwilling, and W. Bode, Refined 1.8 A X-ray crystal structure of astacin, a zinc-endopeptidase from the crayfish Astacus astacus L. Structure determination, refinement, molecular structure and comparison with thermolysin, J. Mol. Biol, vol.229, pp.945-968, 1993.

R. S. Gomolka, A. Cudnoch-jedrzejewska, K. Czarzasta, and E. Szczepanska-sadowska, Reduction of pressor response to stress by centrally acting apelin in spontaneously hypertensive rats, J Basic Clin Physiol Pharmacol, vol.26, pp.233-236, 2015.

E. M. Gordon, J. D. Godfrey, N. G. Delaney, M. M. Asaad, D. Von-langen et al., Design of novel inhibitors of aminopeptidases. Synthesis of peptide-derived diamino thiols and sulfur replacement analogues of bestatin, J. Med. Chem, vol.31, pp.2199-2211, 1988.

J. P. Gorvel, A. Benajiba, and S. Maroux, Purification and characterization of the rabbit intestinal brush-border aminopeptidase A, Biochim. Biophys. Acta, vol.615, pp.271-274, 1980.

R. Gossrau, H. J. Merker, T. Günther, R. Graf, and J. Vormann, Enzymatic and morphological response of the thymus to drugs in normal and zinc-deficient pregnant rats and their fetuses, Histochemistry, vol.86, pp.321-329, 1987.

L. Gouzènes, M. G. Desarménien, N. Hussy, P. Richard, and F. C. Moos, Vasopressin regularizes the phasic firing pattern of rat hypothalamic magnocellular vasopressin neurons, J. Neurosci, vol.18, pp.1879-1885, 1998.

E. M. Grau, G. V. Marathe, and S. S. Tate, Rapid purification of rat kidney brush borders enriched in gamma-glutamyl transpeptidase, FEBS Lett, vol.98, pp.91-95, 1979.

V. Gregorc, F. G. De-braud, T. M. De-pas, R. Scalamogna, G. Citterio et al., Phase I study of NGR-hTNF, a selective vascular targeting agent, in combination with cisplatin in refractory solid tumors, Clin. Cancer Res, vol.17, 1964.

V. Gregorc, P. A. Zucali, A. Santoro, G. L. Ceresoli, G. Citterio et al., Phase II study of asparagine-glycine-arginine-human tumor necrosis factor alpha, a selective vascular targeting agent, in previously treated patients with malignant pleural mesothelioma, J. Clin. Oncol, vol.28, pp.2604-2611, 2010.

P. &. Ggiffiths, &. J. Lolait, L. E. Hais, and J. F. Pato, Vasopressin v1a receptors mediate the hypertensive effects of [PyrNaN]apelin-13 in the rat rostral ventrolateral medulla, J. Physiol, 2017.

C. Gros, B. Giros, and J. C. Schwartz, Purification of membrane-bound aminopeptidase from rat brain: identification of aminopeptidase M, Neuropeptides, vol.5, pp.485-488, 1985.

C. Gros, B. Giros, J. C. Schwartz, A. Vlaiculescu, J. Costentin et al., Potent inhibition of cerebral aminopeptidases by carbaphethiol, a parenterally active compound, Neuropeptides, vol.12, pp.111-118, 1988.

C. Gros, B. Solhonne, B. Giros, H. Pollard, N. Salès et al., Immunohistochemical and subcellular studies of aminopeptidase M localization in rat brain: microvessels and synaptic membranes, NIDA Res. Monogr, vol.75, pp.303-306, 1986.

J. Gundry, R. Glenn, P. Alagesan, and S. Rajagopal, A Practical Guide to Approaching Biased Agonism at G Protein Coupled Receptors, Front Neurosci, vol.11, p.17, 2017.

Y. Habata, R. Fujii, M. Hosoya, S. Fukusumi, Y. Kawamata et al., Apelin, the natural ligand of the orphan receptor APJ, is abundantly secreted in the colostrum, Biochim. Biophys. Acta, vol.1452, pp.25-35, 1999.

E. Hackenthal, R. Hackenthal, and K. G. Hofbauer, Evidence against inhibition of the reninaminopeptidase M in rat brain and periphery: relationship of enzyme localization and enkephalin metabolism, Peptides, vol.8, pp.523-532, 1976.

C. M. Herzig, W. Schoeppe, and J. E. Scherberich, Angiotensinase A (aminopeptidase A): properties of chromatographically purified isoforms from human kidney, J. Chromatogr, vol.625, pp.73-82, 1992.

J. R. Hesp and N. M. Hooper, Proteolytic fragmentation reveals the oligomeric and domain structure of porcine aminopeptidase A, Biochemistry, vol.36, pp.3000-3007, 1997.

J. B. Higgins and P. J. Casey, In vitro processing of recombinant G protein gamma subunits. Requirements for assembly of an active beta gamma complex, J. Biol. Chem, vol.269, pp.9067-9073, 1994.

J. D. Hildebrandt, R. D. Sekura, J. Codina, R. Iyengar, C. R. Manclark et al., Stimulation and inhibition of adenylyl cyclases mediated by distinct regulatory proteins, Nature, vol.302, pp.706-709, 1983.

U. Hilgenfeldt, Angiotensinogen in rat cerebrospinal fluid, Clin Exp Hypertens A, vol.6, pp.1815-1824, 1984.

S. Hirose, H. Yokosawa, and T. Inagami, Immunochemical identification of renin in rat brain and distinction from acid proteases, Nature, vol.274, pp.392-393, 1978.

D. C. Hogarty, E. A. Speakman, V. Puig, and M. I. Phillips, The role of angiotensin, AT1 and AT2 receptors in the pressor, drinking and vasopressin responses to central angiotensin, Brain Res, vol.586, pp.289-294, 1992.

H. M. Holden, D. E. Tronrud, A. F. Monzingo, L. H. Weaver, and B. W. Matthews, Slow-and fast-binding inhibitors of thermolysin display different modes of binding: crystallographic analysis of extended phosphonamidate transition-state analogues, Biochemistry, vol.26, pp.8542-8553, 1987.

K. Hollenstein, J. Kean, A. Bortolato, R. K. Cheng, A. S. Doré et al., Structure of class B GPCR corticotropin-releasing factor receptor 1, Nature, vol.499, pp.438-443, 2013.

M. A. Holmes and B. W. Matthews, Binding of hydroxamic acid inhibitors to crystalline thermolysin suggests a pentacoordinate zinc intermediate in catalysis, Biochemistry, vol.20, pp.6912-6920, 1981.

J. E. Hoogendijk, E. Fliers, D. F. Swaab, and R. W. Verwer, Activation of vasopressin neurons in the human supraoptic and paraventricular nucleus in senescence and senile dementia, J. Neurol. Sci, vol.69, pp.291-299, 1985.

N. M. Hooper, Families of zinc metalloproteases, FEBS Lett, vol.354, pp.1-6, 1994.

V. K. Hopsu, U. M. Kantonen, and G. G. Glenner, A PEPTIDASE FROM RAT TISSUES SELECTIVELY HYDROLYZING N-TERMINAL ARGININE AND LYSINE RESIDUES, Life Sciences, vol.3, pp.1449-1453, 1962.

V. K. Hopsu, K. K. Mäkinn, and G. G. Glenner, Characterization of aminopeptidase B: substrate specificity and affector studies, Arch. Biochem. Biophys, vol.114, pp.567-575, 1966.

T. Hori, T. Kumasaka, M. Yamamoto, N. Nonaka, N. Tanaka et al., ttuutuueà ofà aà eeà aspziià etalloeedopeptidaseà ffooà GGifolaà foodosa:à implications for the catalytic mechanism and substrate specificity based on several different crystal forms, Acta Crystallogr. D Biol. Crystallogr, vol.57, pp.361-368

F. Horn, E. Bettler, L. Oliveira, F. Campagne, F. E. Cohen et al., GPCRDB information system for G protein-coupled receptors, Nucleic Acids Res, vol.31, pp.294-297, 2003.
URL : https://hal.archives-ouvertes.fr/hal-00313146

F. Horn, J. Weare, M. W. Beukers, S. Hörsch, A. Bairoch et al., GPCRDB: an information system for G protein-coupled receptors, Nucleic Acids Res, vol.26, pp.275-279, 1998.

M. Hosoya, Y. Kawamata, S. Fukusumi, R. Fujii, Y. Habata et al., Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin, J. Biol. Chem, vol.275, pp.21061-21067, 2000.

J. Howl and M. Wheatley, Molecular recognition of peptide and non-peptide ligands by the extracellular domains of neurohypophysial hormone receptors, Biochem. J, vol.317, pp.577-582, 1996.

H. Huang, J. F. Arnal, C. Llorens-cortes, M. Challah, F. Alhenc-gelas et al., Discrepancy between plasma and lung angiotensin-converting enzyme activity in experimental congestive heart failure. A novel aspect of endothelium dysfunction, Circ. Res, vol.75, pp.454-461, 1994.

R. P. Hughey, B. B. Rankin, J. S. Elce, and N. P. Curthoys, Specificity of a particulate rat renal peptidase and its localization along with other enzymes of mercapturic acid synthesis, Arch. Biochem. Biophys, vol.186, pp.211-217, 1978.

A. Hurbin, L. Boissin-agasse, H. Orcel, A. Rabié, N. Joux et al., The V1a and V1b, but not V2, vasopressin receptor genes are expressed in the supraoptic nucleus of the rat hypothalamus, and the transcripts are essentially colocalized in the vasopressinergic magnocellular neurons, Endocrinology, vol.139, pp.4701-4707, 1998.

A. Husain, R. R. Smeby, D. Wilk, V. J. Dzau, and F. M. Bumpus, Biochemical and immunological properties of dog brain isorenin, Endocrinology, vol.114, pp.2210-2215, 1984.

A. Hus-citharel, L. Bodineau, A. Frugière, F. Joubert, N. Bouby et al., Apelin counteracts vasopressin-induced water reabsorption via cross talk between apelin and vasopressin receptor signaling pathways in the rat collecting duct, Endocrinology, vol.155, pp.4483-4493, 2014.

A. Hus-citharel, N. Bouby, A. Frugière, L. Bodineau, J. Gasc et al., Effect of apelin on glomerular hemodynamic function in the rat kidney, Kidney Int, vol.74, pp.486-494, 2008.
URL : https://hal.archives-ouvertes.fr/inserm-00422663

A. Hus-citharel, J. M. Gasc, S. Zini, J. Marchetti, B. Roques et al., Aminopeptidase A activity and angiotensin III effects on [Ca2+]i along the rat nephron, Kidney Int, vol.56, pp.850-859, 1999.

S. Hwang and V. Hook, Zinc regulation of aminopeptidase B involved in neuropeptide production, FEBS Lett, vol.582, pp.2527-2531, 2008.

S. Hwang and &. , àHook,àV.,à.à"eeetoooàesileàaaiopeptidaseà B related to neuropeptide processing: molecular identification and subcellular localization to enkephalin-and NPY-containing chromaffin granules, J. Neurochem, vol.100, pp.1340-1350

N. Ikeda, Y. Nakajima, T. Tokuhara, N. Hattori, M. Sho et al., Clinical significance of aminopeptidase N/CD13 expression in human pancreatic carcinoma, Clin. Cancer Res, vol.9, pp.1503-1508, 2003.

Y. Inagaki, W. Tang, L. Zhang, G. Du, W. Xu et al., Novel aminopeptidase N (APN/CD13) inhibitor 24F can suppress invasion of hepatocellular carcinoma cells as well as angiogenesis, Biosci Trends, vol.4, pp.56-60, 2010.

T. Inagami, M. R. Celio, D. L. Clemens, D. Lau, Y. Takii et al., Renin in rat and mouse brain: immunohistochemical identification and localization, Clin. Sci, 1980.

N. Inguimbert, P. Coric, H. Dhotel, E. Bonnard, C. Llorens-cortes et al., Synthesis and in vitro activities of new non-peptidic APA inhibitors, J. Pept. Res, vol.65, pp.175-188, 2005.

A. D. Intebi, M. S. Flaxman, W. F. Ganong, and C. F. Deschepper, Angiotensinogen production by rat astroglial cells in vitro and in vivo, Neuroscience, vol.34, pp.545-554, 1990.

V. Isberg, C. De-graaf, A. Bortolato, V. Cherezov, V. Katritch et al., Generic GPCR residue numbersaligning topology maps while minding the gaps, Trends Pharmacol. Sci, vol.36, pp.22-31, 2015.

J. Ishida, T. Hashimoto, Y. Hashimoto, S. Nishiwaki, T. Iguchi et al., Regulatory roles for APJ, a seventransmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo, J. Biol. Chem, vol.279, pp.26274-26279, 2004.

T. Isobe and T. Okuyama, Brain micro glutamic acid-rich protein is the C-terminal endpiece of the neurofilament 68-kDa protein as determined by the primary sequence, FEBS Lett, vol.182, pp.389-392, 1985.

K. Ito, Y. Nakajima, Y. Onohara, M. Takeo, K. Nakashima et al., Crystal structure of aminopeptidase N (proteobacteria alanyl aminopeptidase) from Escherichia coli and conformational change of methionine 260 involved in substrate recognition, J. Biol. Chem, vol.281, pp.33664-33676, 2006.

X. Iturrioz, R. Alvear-perez, N. De-mota, C. Franchet, F. Guillier et al., Identification and pharmacological properties of E339-3D6, the first nonpeptidic apelin receptor agonist, FASEB J, vol.24, pp.1506-1517, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00547967

X. Iturrioz, R. Gerbier, V. Leroux, R. Alvear-perez, B. Maigret et al., By interacting with the C-terminal Phe of apelin, Phe255 and Trp259 in helix VI of the apelin receptor are critical for internalization, J. Biol. Chem, vol.285, pp.32627-32637, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00547969

X. Iturrioz, R. Rozenfeld, A. Michaud, P. Corvol, and C. Llorens-cortes, Study of asparagine 353 in aminopeptidase A: characterization of a novel motif (GXMEN) implicated in exopeptidase specificity of monozinc aminopeptidases, Biochemistry, vol.40, pp.14440-14448, 2001.

X. Iturrioz, G. Vazeux, J. Célérier, P. Corvol, and C. Llorens-cortès, Histidine 450 plays a critical role in catalysis and, with Ca2+, contributes to the substrate specificity of aminopeptidase A, Biochemistry, vol.39, pp.3061-3068, 2000.

Y. Iwanaga, Y. Kihara, H. Takenaka, and T. Kita, Down-regulation of cardiac apelin system in hypertrophied and failing hearts: Possible role of angiotensin II-angiotensin type 1 receptor system, J. Mol. Cell. Cardiol, vol.41, pp.798-806, 2006.

A. G. Japp, N. L. Cruden, D. A. Amer, V. K. Li, E. B. Goudie et al., Vascular effects of apelin in vivo in man, J. Am. Coll. Cardiol, vol.52, pp.908-913, 2008.

A. G. Japp, N. L. Cruden, G. Barnes, N. Van-gemeren, J. Mathews et al., Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure, Circulation, vol.121, pp.1818-1827, 2010.

A. G. Japp and D. E. Newby, The apelin-APJ system in heart failure: pathophysiologic relevance and therapeutic potential, Biochem. Pharmacol, vol.75, pp.1882-1892, 2008.
DOI : 10.1016/j.bcp.2007.12.015

M. B. Jarpe, C. Knall, F. M. Mitchell, A. M. Buhl, E. Duzic et al., Leu11]Substance P acts as a biased agonist toward neuropeptide and chemokine receptors, J. Biol. Chem, vol.9, pp.3097-3104, 1998.
DOI : 10.1074/jbc.273.5.3097

L. L. Jensen, J. W. Harding, and J. W. Wright, Increased blood pressure induced by central application of aminopeptidase inhibitors is angiotensinergic-dependent in normotensive and hypertensive rat strains, Brain Res, vol.490, pp.48-55, 1989.

E. Jéquier and F. Constant, Water as an essential nutrient: the physiological basis of hydration, Eur J Clin Nutr, vol.64, pp.115-123, 2010.

Y. Jia, C. Pan, J. Zhang, B. Geng, J. Zhao et al., Apelin protects myocardial injury induced by isoproterenol in rats, Regul. Pept, vol.133, pp.147-154, 2006.
DOI : 10.1016/j.regpep.2005.09.033

Z. Q. Jia, L. Hou, A. Leger, I. Wu, A. B. Kudej et al., Cardiovascular effects of a PEGylated apelin, Peptides, vol.38, pp.181-188, 2012.
DOI : 10.1016/j.peptides.2012.09.003

A. K. Johnson, J. T. Cunningham, and R. L. Thunhorst, Integrative role of the lamina terminalis in the regulation of cardiovascular and body fluid homeostasis, Clin. Exp. Pharmacol. Physiol, vol.23, pp.183-191, 1996.

O. Jöhren, H. Imboden, W. Häuser, I. Maye, G. L. Sanvitto et al., Localization of angiotensin-converting enzyme, angiotensin II, angiotensin II receptor subtypes, and vasopressin in the mouse hypothalamus, Brain Res, vol.757, pp.218-227, 1997.

J. C. Jones, J. W. Duffy, M. Machius, B. R. Temple, H. G. Dohlman et al., The crystal structure of a self-activating G protein alpha subunit reveals its distinct mechanism of signal initiation, Sci Signal, vol.4, 2011.

C. V. Jongeneel, J. Bouvier, and A. Bairoch, A unique signature identifies a family of zincdependent metallopeptidases, FEBS Lett, vol.242, pp.211-214, 1989.

C. Juhl, S. Els-heindl, R. Schönauer, G. Redlich, E. Haaf et al., Development of Potent and Metabolically Stable APJ Ligands with High Therapeutic Potential, 2016.

S. Julius, N. Schork, and A. Schork, Sympathetic hyperactivity in early stages of hypertension: the Ann Arbor data set, J. Cardiovasc. Pharmacol, vol.12, pp.121-129, 1988.

M. Kadekaro, J. Y. Summy-long, S. Freeman, J. S. Harris, M. L. Terrell et al., Cerebral metabolic responses and vasopressin and oxytocin secretions during progressive water deprivation in rats, Am. J. Physiol, vol.262, pp.310-317, 1992.
DOI : 10.1152/ajpregu.1992.262.1.r161-r

R. Kageyama, H. Ohkubo, and S. Nakanishi, Primary structure of human preangiotensinogen deduced from the cloned cDNA sequence, Biochemistry, vol.23, pp.3603-3609, 1984.

S. Kagiyama, M. Fukuhara, K. Matsumura, Y. Lin, K. Fujii et al., Central and peripheral cardiovascular actions of apelin in conscious rats, Regul. Pept, vol.125, pp.55-59, 2005.

Y. Kang, . Kim, . Jongmin, J. P. Anderson, J. Wu et al., Apelin-APJ signaling is a critical regulator of endothelial MEF2 activation in cardiovascular development, Circ. Res, vol.113, pp.22-31, 2013.

Y. Kang, X. E. Zhou, X. Gao, Y. He, W. Liu et al., Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser, vol.523, pp.561-567, 2015.
DOI : 10.2210/pdb4zwj/pdb

URL : http://europepmc.org/articles/pmc4521999?pdf=render

V. Katritch, V. Cherezov, and R. C. Stevens, Structure-function of the G protein-coupled receptor superfamily, Annu. Rev. Pharmacol. Toxicol, vol.53, pp.531-556, 2013.

S. D. Katugampola, J. J. Maguire, S. R. Matthewson, and A. P. Davenport, 125)I](Pyr(1))Apelin-13 is a novel radioligand for localizing the APJ orphan receptor in human and rat tissues with evidence for a vasoconstrictor role in man, Br. J. Pharmacol, vol.132, pp.1255-1260, 2001.

A. M. Katz and B. H. Lorell, Regulation of cardiac contraction and relaxation, Circulation, vol.102, pp.69-74, 2000.
DOI : 10.1161/01.cir.102.suppl_4.iv-69

Y. Kawamata, Y. Habata, S. Fukusumi, M. Hosoya, R. Fujii et al., Molecular properties of apelin: tissue distribution and receptor binding, Biochim. Biophys. Acta, vol.1538, pp.162-171, 2001.

J. Kawamura, Y. Shimada, H. Kitaichi, I. Komoto, Y. Hashimoto et al., Clinicopathological significance of aminopeptidase N/CD13 expression in human gastric carcinoma, Hepatogastroenterology, vol.54, pp.36-40, 2007.

A. Kehlen, U. Lendeckel, H. Dralle, J. Langner, and C. Hoang-vu, Biological significance of aminopeptidase N/CD13 in thyroid carcinomas, Cancer Res, vol.63, pp.8500-8506, 2003.

E. Kelly, T. A. Rooney, and S. R. Nahorski, Pertussis toxin separates two muscarinic receptoreffector mechanisms in the striatum, Eur. J. Pharmacol, vol.119, pp.129-130, 1985.

T. Kenakin, Agonist-receptor efficacy. II. Agonist trafficking of receptor signals, Trends Pharmacol. Sci, vol.16, pp.232-238, 1995.

T. P. Kenakin and P. H. Morgan, Theoretical effects of single and multiple transducer receptor coupling proteins on estimates of the relative potency of agonists, Mol. Pharmacol, vol.35, pp.214-222, 1989.

P. A. Khairallah, F. M. Bumpus, I. H. Page, and R. R. Smeby, Angiotensinase with a high degree of specificity in plasma and red cells, Science, vol.140, pp.672-674, 1963.

P. Khan, P. R. Maloney, M. Hedrick, P. Gosalia, M. Milewski et al., Probe Reports from the NIH Molecular Libraries Program. National Center for Biotechnology Information (US), 2010.

S. M. Khan, R. Sleno, S. Gora, P. Zylbergold, J. Laverdure et al., The expanding roles of G?? subunits in G protein-coupled receptor signaling and drug action, Pharmacol. Rev, vol.65, pp.545-577, 2013.

H. M. Kim, D. R. Shin, O. J. Yoo, H. Lee, and J. Lee, Crystal structure of Drosophila angiotensin I-converting enzyme bound to captopril and lisinopril, FEBS Lett, vol.538, pp.65-70, 2003.

M. J. Kleinz and A. P. Davenport, Immunocytochemical localization of the endogenous vasoactive peptide apelin to human vascular and endocardial endothelial cells, Regul. Pept, vol.118, pp.119-125, 2004.

M. J. Kleinz, J. N. Skepper, and A. P. Davenport, Immunocytochemical localisation of the apelin receptor, APJ, to human cardiomyocytes, vascular smooth muscle and endothelial cells, Regul. Pept, vol.126, pp.233-240, 2005.

T. A. Kohout, F. S. Lin, S. J. Perry, D. A. Conner, and R. J. Lefkowitz, beta-Arrestin 1 and 2 differentially regulate heptahelical receptor signaling and trafficking, Proc. Natl. Acad. Sci. U.S.A, vol.98, pp.1601-1606, 2001.

L. F. Kolakowski, GCRDb: a G-protein-coupled receptor database, Recept. Channels, vol.2, pp.1-7, 1994.

K. Kuba, L. Zhang, Y. Imai, S. Arab, M. Chen et al., Impaired heart contractility in Apelin gene-deficient mice associated with aging and pressure overload, Circ. Res, vol.101, pp.32-42, 2007.

T. Kubo, H. Yamaguchi, M. Tsujimura, Y. Hagiwara, and R. Fukumori, Blockade of angiotensin receptors in the anterior hypothalamic preoptic area lowers blood pressure in DOCA-salt hypertensive rats, Hypertens. Res, vol.23, pp.109-118, 2000.

P. Kugler, Aminopeptidase A is angiotensinase A. II. Biochemical studies on aminopeptidase A and M in rat kidney homogenate, Histochemistry, vol.74, pp.247-261, 1982.

P. Kugler, Localization of aminopeptidase A (angiotensinase A) in the rat and mouse kidney, Histochemistry, vol.72, pp.269-278, 1981.

P. Kumar, A. Ashokan, and G. K. Aradhyam, Apelin binding to human APJ receptor leads to biased signaling, Biochim. Biophys. Acta, vol.1864, pp.1748-1756, 2016.

J. Kunz, D. Krause, M. Kremer, and R. Dermietzel, The 140-kDa protein of blood-brain barrier-associated pericytes is identical to aminopeptidase N, J. Neurochem, vol.62, pp.2375-2386, 1994.

O. Kurauchi, S. Mizutani, K. Okano, O. Narita, and Y. Tomoda, Purification and characterization of human placental microsomal aminopeptidase: immunological difference between placental microsomal aminopeptidase and pregnancy serum cystyl-aminopeptidase, Enzyme, vol.35, pp.197-205, 1986.
DOI : 10.1159/000469343

R. Ladeiras-lopes, J. Ferreira-martins, and A. F. Leite-moreira, The apelinergic system: the role played in human physiology and pathology and potential therapeutic applications, Arq. Bras. Cardiol, vol.90, pp.343-349, 2008.

K. Lalu, S. Lampelo, M. Nummelin-kortelainen, and T. Vanha-perttula, Purification and partial characterization of aminopeptidase A from the serum of pregnant and non-pregnant women, Biochim. Biophys. Acta, vol.789, pp.324-333, 1984.

K. Lalu, S. Lampelo, and T. Vanha-perttula, Characterization of three aminopeptidases purified from maternal serum, Biochim. Biophys. Acta, vol.873, pp.190-197, 1986.

K. Lalu, S. Lampelo, and T. Vanha-perttula, Purification of three aminopeptidases from human maternal serum, Int. J. Biochem, vol.17, pp.1227-1235, 1985.

D. G. Lambright, J. Sondek, A. Bohm, N. P. Skiba, H. E. Hamm et al., The 2.0 A crystal structure of a heterotrimeric G protein, Nature, vol.379, pp.311-319, 1996.

D. N. Langelaan, T. Reddy, A. W. Banks, G. Dellaire, D. J. Dupré et al., Structural features of the apelin receptor N-terminal tail and first transmembrane segment implicated in ligand binding and receptor trafficking, Biochim. Biophys. Acta, vol.1828, pp.1471-1483, 2013.

S. A. Laporte, R. H. Oakley, J. A. Holt, L. S. Barak, and M. G. Caron, The interaction of betaarrestin with the AP-2 adaptor is required for the clustering of beta 2-adrenergic receptor into clathrin-coated pits, J. Biol. Chem, vol.275, pp.23120-23126, 2000.

J. L. Lavoie, M. D. Cassell, K. W. Gross, and C. D. Sigmund, Localization of renin expressing cells in the brain, by use of a REN-eGFP transgenic model, Physiol. Genomics, vol.16, pp.240-246, 2004.

L. Moual, H. Devault, A. Roques, B. P. Crine, P. Boileau et al., Identification of glutamic acid 646 as a zinc-coordinating residue in endopeptidase-24.11, J. Biol. Chem, vol.266, pp.15670-15674, 1991.

L. Moual, H. Dion, N. Roques, B. P. Crine, P. Boileau et al., Asp650 is crucial for catalytic activity of neutral endopeptidase 24-11, Eur. J. Biochem, vol.221, pp.475-480, 1994.

C. Lee, W. Lü, J. C. Michel, A. Goehring, J. Du et al., NMDA receptor structures reveal subunit arrangement and pore architecture, Nature, vol.511, pp.191-197, 2014.
DOI : 10.1038/nature13548

URL : http://europepmc.org/articles/pmc4263351?pdf=render

D. K. Lee, R. Cheng, T. Nguyen, T. Fan, A. P. Kariyawasam et al., OODod,àB.F.,à.àChaaateeizatioàofàapeli,àtheàligand for the APJ receptor, J. Neurochem, vol.74, pp.34-41

À. K. Lee, &. , &. &. , and .. F. , à.àTheàfateàofàtheàiteealizedàapelià receptor is determined by different isoforms of apelin mediating differential interaction with beta-arrestin, Biochem. Biophys. Res. Commun, vol.395, pp.185-189

À. K. Lee, .. &. , &. , &. &. , and .. F. , à.àModifiatiooà of the terminal residue of apelin-13 antagonizes its hypotensive action, Endocrinology, vol.146, pp.231-236

H. J. Lee, M. Tomioka, Y. Takaki, H. Masumoto, and T. C. Saido, Molecular cloning and expression of aminopeptidase A isoforms from rat hippocampus, Biochim. Biophys. Acta, vol.1493, pp.273-278, 2000.

M. Lee, K. M. Appleton, E. G. Strungs, J. Y. Kwon, T. A. Morinelli et al., The conformational signature of ?-arrestin2 predicts its trafficking and signalling functions, Nature, vol.531, pp.665-668, 2016.

M. A. Lee-kirsch, F. Gaudet, M. C. Cardoso, and K. Lindpaintner, Distinct renin isoforms generated by tissue-specific transcription initiation and alternative splicing, Circ. Res, vol.84, pp.240-246, 1999.
DOI : 10.1161/01.res.84.2.240

D. M. Lehmann, A. M. Seneviratne, and A. V. Smrcka, Small molecule disruption of G protein beta gamma subunit signaling inhibits neutrophil chemotaxis and inflammation, Mol. Pharmacol, vol.73, pp.410-418, 2008.
DOI : 10.1124/mol.107.041780

URL : http://europepmc.org/articles/pmc2742223?pdf=render

B. Lejczak, M. P. De-choszczak, and P. Kafarski, Inhibition of aminopeptidases by phosphonic acid and phosphinic acid analogues of aspartic and glutamic acids, J. Enzym. Inhib, vol.7, pp.97-103, 1993.

Z. Lenkei, M. Palkovits, P. Corvol, and C. Llorens-cortès, Expression of angiotensin type-1 (AT1) and type-2 (AT2) receptor mRNAs in the adult rat brain: a functional neuroanatomical review, Front Neuroendocrinol, vol.18, pp.383-439, 1997.

L. Li, J. Wang, and M. D. Cooper, cDNA cloning and expression of human glutamyl aminopeptidase (aminopeptidase A), Genomics, vol.17, pp.657-664, 1993.

L. Li, Q. Wu, B. L. Barnoski, and M. D. Cooper, High-resolution genetic map of the human glutamyl aminopeptidase gene (ENPEP), Genomics, vol.43, pp.380-383, 1997.

Y. Li, J. Chen, B. Bai, H. Du, Y. Liu et al., Heterodimerization of human apelin and kappa opioid receptors: roles in signal transduction, Cell. Signal, vol.24, pp.991-1001, 2012.

P. J. Lijnen, V. V. Petrov, M. Turner, and R. H. Fagard, Collagen production in cardiac fibroblasts during inhibition of aminopeptidase B, J Renin Angiotensin Aldosterone Syst, vol.6, pp.69-77, 2005.

R. W. Lind and D. Ganten, Neuropeptides in the CNS, in: Handbook of Chemical Neuroanatomy, 1990.

I. Litosch, Decoding G?q signaling, Life Sci, vol.152, pp.99-106, 2016.

C. Llorens-cortès, , 2014.

, Biol Aujourdhui, vol.208, pp.217-224

M. J. Lohse, J. L. Benovic, J. Codina, M. G. Caron, and R. J. Lefkowitz, beta-Arrestin: a protein that regulates beta-adrenergic receptor function, Science, vol.248, pp.1547-1550, 1990.

Z. Lojda and R. Gossrau, Study on aminopeptidase A, Histochemistry, vol.67, pp.267-290, 1980.

Y. Luan, C. Ma, Y. Wang, H. Fang, and W. Xu, The characteristics, functions and inhibitors of three aminopeptidases belonging to the m1 family, Curr. Protein Pept. Sci, vol.13, pp.490-500, 2012.

P. J. Lucassen, A. Salehi, C. W. Pool, N. K. Gonatas, and D. F. Swaab, Activation of asoppessiààeuuoosàiàagigàaadàálzheieeesàdisease, àJ.àNeuuoeedoooiol, vol.6, pp.673-679, 1994.

N. Luciani, C. Marie-claire, E. Ruffet, A. Beaumont, B. P. Roques et al., Characterization of Glu350 as a critical residue involved in the N-terminal amine binding site of aminopeptidase N (EC insights into its mechanism of action, Biochemistry, vol.37, pp.686-692, 1998.
URL : https://hal.archives-ouvertes.fr/inserm-00145193

M. Ludwig, Dendritic release of vasopressin and oxytocin, J. Neuroendocrinol, vol.10, pp.881-895, 1998.

K. R. Lynch, C. L. Hawelu-johnson, and P. G. Guyenet, Localization of brain angiotensinogen mRNA by hybridization histochemistry, Brain Res, vol.388, pp.149-158, 1987.

Y. C. Ma and X. Y. Huang, Novel regulation and function of Src tyrosine kinase, Cell. Mol. Life Sci, vol.59, pp.456-462, 2002.

N. J. Macaluso, S. L. Pitkin, J. J. Maguire, A. P. Davenport, and R. C. Glen, Discovery of a competitive apelin receptor, APJ) antagonist. ChemMedChem, vol.6, pp.1017-1023, 2011.

D. P. Macgregor, C. Murone, K. Song, A. M. Allen, G. Paxinos et al., Angiotensin II receptor subtypes in the human central nervous system, Brain Res, vol.675, pp.231-240, 1995.

J. J. Maguire, M. J. Kleinz, S. L. Pitkin, and A. P. Davenport, Pyr1]apelin-13 identified as the predominant apelin isoform in the human heart: vasoactive mechanisms and inotropic action in disease, Hypertension, vol.54, pp.598-604, 2009.

E. Malito, L. A. Ralat, M. Manolopoulou, J. L. Tsay, N. L. Wadlington et al., Molecular bases for the recognition of short peptide substrates and cysteine-directed modifications of human insulin-degrading enzyme, Biochemistry, vol.47, pp.12822-12834, 2008.

P. R. Maloney, P. Khan, M. Hedrick, P. Gosalia, M. Milewski et al.,

F. Zeng, A. M. Novo, M. Vicchiarelli, J. Diwan, T. D. Chung et al., Functional antagonists of the Apelin (APJ) receptor, in: Probe Reports from the NIH Molecular Libraries Program, National Center for Biotechnology Information (US), 2010.

P. R. Maloney, P. Khan, M. Hedrick, P. Gosalia, M. Milewski et al., Discovery of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221) as a functional antagonist of the apelin (APJ) receptor, Bioorg. Med. Chem. Lett, vol.22, pp.6656-6660, 2012.

M. L. Mangiapane, T. N. Thrasher, L. C. Keil, J. B. Simpson, and W. F. Ganong, Role for the subfornical organ in vasopressin release, Brain Res. Bull, vol.13, pp.43-47, 1984.

M. Manning, J. Lowbridge, J. Haldar, and W. H. Sawyer, Design of neurohypophyseal peptides that exhibit selective agonistic and antagonistic properties, Fed. Proc, vol.36, pp.1848-1852, 1977.

Y. Marc, J. Gao, F. Balavoine, A. Michaud, B. P. Roques et al., Central antihypertensive effects of orally active aminopeptidase A inhibitors in spontaneously hypertensive rats, Hypertension, vol.60, pp.411-418, 2012.

Y. Marc and C. Llorens-cortes, The role of the brain renin-angiotensin system in hypertension: implications for new treatment, Prog. Neurobiol, vol.95, pp.89-103, 2011.

J. Marchetti, S. Roseau, and F. Alhenc-gelas, Angiotensin I converting enzyme and kininhydrolyzing enzymes along the rabbit nephron, Kidney Int, vol.31, pp.744-751, 1987.

J. Margathe, X. Iturrioz, R. Alvear-perez, C. Marsol, S. Riché et al., Structure-activity relationship studies toward the discovery of selective apelin receptor agonists, J. Med. Chem, vol.57, pp.2908-2919, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02153719

C. Marie-claire, B. P. Roques, and A. Beaumont, Intramolecular processing of prothermolysin, J. Biol. Chem, vol.273, pp.5697-5701, 1998.
URL : https://hal.archives-ouvertes.fr/inserm-00145189

C. Marie-claie, E. , &. Beauuoot, À. Á. Oodoohue, M. et al., Evidence by site-directed mutagenesis that arginine 203 of thermolysin and arginine 717 of neprilysin (neutral endopeptidase) play equivalent critical roles in substrate hydrolysis and inhibitor binding, Biochemistry, vol.36, pp.13938-13945, 1997.

A. Mascolo, M. Sessa, C. Scavone, A. De-angelis, C. Vitale et al., New and old roles of the peripheral and brain renin-angiotensinaldosterone system (RAAS): Focus on cardiovascular and neurological diseases, Int. J. Cardiol, vol.227, pp.734-742, 2017.

B. Masri, H. Lahlou, H. Mazarguil, B. Knibiehler, and Y. Audigier, Apelin (65-77) activates extracellular signal-regulated kinases via a PTX-sensitive G protein, Biochem. Biophys. Res. Commun, vol.290, pp.539-545, 2002.

B. Masri, N. Morin, M. Cornu, B. Knibiehler, and Y. Audigier, Apelin (65-77) activates p70 S6 kinase and is mitogenic for umbilical endothelial cells, FASEB J, vol.18, 1909.
URL : https://hal.archives-ouvertes.fr/inserm-00481005

B. Masri, N. Morin, L. Pedebernade, B. Knibiehler, and Y. Audigier, The apelin receptor is coupled to Gi1 or Gi2 protein and is differentially desensitized by apelin fragments, J. Biol. Chem, vol.281, pp.18317-18326, 2006.
URL : https://hal.archives-ouvertes.fr/inserm-00480987

Y. Masuyama, K. Tsuda, M. Kuchii, and I. Nishio, Peripheral neural mechanism of hypertension in rat models-peripheral sympathetic neurotransmission in hypertension, J Hypertens Suppl, vol.4, pp.189-192, 1986.

À. Mmtt, .. N. Bíró, T. Galuska, L. Trencsényi, and G. , In vivo imaging of Aminopeptidase N (CD13) receptors in experimental renal tumors using the novel radiotracer (68)Ga-NOTA-c(NGR), Eur J Pharm Sci, vol.69, pp.61-71, 2015.

I. Mathar, M. Kecskes, G. Van-der-mieren, G. Jacobs, J. E. Camacho-londoño et al., Increased ?adrenergic inotropy in ventricular myocardium from Trpm4-/-mice, Circ. Res, vol.114, pp.283-294, 2014.

R. Matsas, S. L. Stephenson, J. Hryszko, A. J. Kenny, and A. J. Turner, The metabolism of neuropeptides. Phase separation of synaptic membrane preparations with Triton X-114 reveals the presence of aminopeptidase N, Biochem. J, vol.231, pp.445-449, 1985.

B. W. Matthews, Structural basis of the action of thermolysin and related zinc peptidases, Accounts of chemical research, vol.21, pp.333-340, 1988.

B. W. Matthews, P. M. Colman, J. N. Jansonius, K. Titani, K. A. Walsh et al., Structure of thermolysin, Nature New Biol, vol.238, pp.41-43, 1972.

B. W. Matthews, J. N. Jansonius, P. M. Colman, B. P. Schoenborn, and D. Dupourque, Three-dimensional structure of thermolysin, Nature New Biol, vol.238, pp.37-41, 1972.

B. W. Matthews, L. H. Weaver, and W. R. Kester, The conformation of thermolysin, J. Biol. Chem, vol.249, pp.8030-8044, 1974.

A. Mauborgne, S. Bourgoin, J. J. Benoliel, M. Hirsch, J. L. Berthier et al., Enkephalinase is involved in the degradation of endogenous substance P released from slices of rat substantia nigra, J. Pharmacol. Exp. Ther, vol.243, pp.674-680, 1987.

L. T. May, K. Leach, P. M. Sexton, and A. Christopoulos, Allosteric modulation of G proteincoupled receptors, Annu. Rev. Pharmacol. Toxicol, vol.47, pp.1-51, 2007.

R. M. Mcallen, G. L. Pennington, and M. J. Mckinley, Osmoresponsive units in sheep median preoptic nucleus, Am. J. Physiol, vol.259, pp.593-600, 1990.

W. E. Mcintire, G. Maccleery, and J. C. Garrison, The G protein beta subunit is a determinant in the coupling of Gs to the beta 1-adrenergic and A2a adenosine receptors, J. Biol. Chem, vol.276, pp.15801-15809, 2001.

D. B. Mckay, M. M. Thayer, K. M. Flaherty, H. Pley, and D. Benvegnu, Crystallographic structures of the elastase of Pseudomonas aeruginosa, Matrix Suppl, vol.1, pp.112-115, 1992.

S. M. Mckinnie, C. Fischer, K. M. Tran, W. Wang, F. Mosquera et al., The Metalloprotease Neprilysin Degrades and Inactivates Apelin Peptides, Chembiochem, vol.17, pp.1495-1498, 2016.

A. D. Medhurst, C. A. Jennings, M. J. Robbins, R. P. Davis, C. Ellis et al., Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin, J. Neurochem, vol.84, pp.1162-1172, 2003.

J. F. Medina, A. Wetterholm, O. Rådmark, R. Shapiro, J. Z. Haeggström et al., Leukotriene A4 hydrolase: determination of the three zinc-binding ligands by site-directed mutagenesis and zinc analysis, Proc. Natl. Acad. Sci. U.S.A, vol.88, pp.7620-7624, 1991.

T. Meinnel, S. Blanquet, and F. Dardel, A new subclass of the zinc metalloproteases superfamily revealed by the solution structure of peptide deformylase, J. Mol. Biol, vol.262, pp.375-386, 1996.

T. Meinnel, C. Lazennec, and S. Blanquet, Mapping of the active site zinc ligands of peptide deformylase, J. Mol. Biol, vol.254, pp.175-183, 1995.

J. V. Menani, D. S. Colombari, T. G. Beltz, R. L. Thunhorst, and A. K. Johnson, Salt appetite: interaction of forebrain angiotensinergic and hindbrain serotonergic mechanisms, Brain Res, vol.801, pp.29-35, 1998.

J. Ménard, J. Bouhnik, E. Clauser, J. P. Richoux, and P. Corvol, Biochemistry and regulation of angiotensinogen, Clin Exp Hypertens A, vol.5, pp.1005-1019, 1983.

F. A. Mendelsohn, Localization of angiotensin converting enzyme in rat forebrain and other tissues by in vitro autoradiography using 125I-labelled MK351A, Clin. Exp. Pharmacol. Physiol, vol.11, pp.431-435, 1984.

F. A. Mendelsohn, S. Y. Chai, and M. Dunbar, In vitro autoradiographic localization of angiotensin-converting enzyme in rat brain using 125I-labelled MK351A, J Hypertens Suppl, vol.2, pp.41-44, 1984.

S. Mentzel, H. B. Dijkman, J. P. Van-son, R. A. Koene, and K. J. Assmann, Organ distribution of aminopeptidase A and dipeptidyl peptidase IV in normal mice, J. Histochem. Cytochem, vol.44, pp.445-461, 1996.

J. M. Meyer, D. L. Felten, and J. A. Weyhenmeyer, Levels of immunoreactive angiotensin II in microdissected nuclei from adult WKY and SH rat brain, Clin Exp Hypertens A, vol.11, pp.103-117, 1989.

M. Migaud, C. Durieux, J. Viereck, E. Soroca-lucas, M. C. Fournié-zaluski et al., The in vivo metabolism of cholecystokinin (CCK-8) is essentially ensured by aminopeptidase A, Peptides, vol.17, pp.601-607, 1996.
URL : https://hal.archives-ouvertes.fr/hal-01602909

M. A. Millan, D. M. Jacobowitz, G. Aguilera, and K. J. Catt, Differential distribution of AT1 and AT2 angiotensin II receptor subtypes in the rat brain during development, Proc. Natl. Acad. Sci. U.S.A, vol.88, pp.11440-11444, 1991.

R. D. Minshall, C. Tiruppathi, S. M. Vogel, and A. B. Malik, Vesicle formation and trafficking in endothelial cells and regulation of endothelial barrier function, Histochem. Cell Biol, vol.117, pp.105-112, 2002.

À. Modgil and &. T. , uu,àC.,à.àápeli-13 inhibits large-conductance Ca2+activated K+ channels in cerebral artery smooth muscle cells via a PI3-kinase dependent mechanism, PLoS ONE, vol.8, p.83051

A. F. Monzingo and B. W. Matthews, Binding of N-carboxymethyl dipeptide inhibitors to thermolysin determined by X-ray crystallography: a novel class of transition-state analogues for zinc peptidases, Biochemistry, vol.23, pp.5724-5729, 1984.

N. G. Morgenthaler, J. Struck, S. Jochberger, and M. W. Dünser, Copeptin: clinical use of a new biomarker, Trends Endocrinol. Metab, vol.19, pp.43-49, 2008.

B. J. Morris and I. A. Reid, The distribution of angiotensinogen in dog brain studied by cell fractionation, Endocrinology, vol.103, pp.492-500, 1978.

T. Murayama and M. Ui, Receptor-mediated inhibition of adenylate cyclase and stimulation of arachidonic acid release in 3T3 fibroblasts. Selective susceptibility to isletactivating protein, pertussis toxin, J. Biol. Chem, vol.260, pp.7226-7233, 1985.

A. Murza, K. Belleville, J. Longpré, P. Sarret, and É. Marsault, Stability and degradation patterns of chemically modified analogs of apelin-13 in plasma and cerebrospinal fluid, Biopolymers, vol.102, pp.297-303, 2014.

A. Murza, É. Besserer-offroy, J. Côté, P. Bérubé, J. Longpré et al., C-Terminal modifications of apelin13 significantly change ligand binding, receptor signaling, and hypotensive action, J. Med. Chem, vol.58, pp.2431-2440, 2015.

A. Murza, A. Parent, E. Besserer-offroy, H. Tremblay, F. Karadereye et al., Elucidation of the structure-activity relationships of apelin: influence of unnatural amino acids on binding, signaling, and plasma stability, ChemMedChem, vol.7, pp.318-325, 2012.

A. Murza, X. Sainsily, D. Coquerel, J. Côté, P. Marx et al., Discovery and Structure-Activity Relationship of a Bioactive Fragment of ELABELA that Modulates Vascular and Cardiac Functions, J. Med. Chem, vol.59, pp.2962-2972, 2016.

A. Murza, X. Sainsily, J. Côté, L. Bruneau-cossette, É. Besserer-offroy et al., Structure-activity relationship of novel macrocyclic biased apelin receptor agonists, Org. Biomol. Chem, vol.15, pp.449-458, 2017.
DOI : 10.1039/c6ob02247b

K. Nagano, J. Ishida, M. Unno, T. Matsukura, and A. Fukamizu, Apelin elevates blood pressure in ICR mice with L-NAME-induced endothelial dysfunction, Mol Med Rep, vol.7, pp.1371-1375, 2013.

S. Nagata, J. Kato, K. Sasaki, N. Minamino, T. Eto et al., Isolation and identification of proangiotensin-12, a possible component of the renin-angiotensin system, Biochem. Biophys. Res. Commun, vol.350, pp.1026-1031, 2006.

I. Nagatsu, T. Nagatsu, T. Yamamoto, G. G. Glenner, and J. W. Mehl, Purification of aminopeptidase A in human serum and degradation of angiotensin II by the purified enzyme, Biochim. Biophys. Acta, vol.198, pp.255-270, 1970.

T. Nakagawa, J. Akaki, R. Satou, M. Takaya, H. Iwata et al., The His-Pro-Phe motif of angiotensinogen is a crucial determinant of the substrate specificity of renin, Biol. Chem, vol.388, pp.237-246, 2007.

T. Nakamura, M. Yamazato, A. Ishida, and Y. Ohya, Excess of Aminopeptidase A in the Brain Elevates Blood Pressure via the Angiotensin II Type 1 and Bradykinin B2 Receptors without Dipsogenic Effect, Int J Hypertens, p.3967595, 2017.

P. Nambi, J. R. Peters, D. R. Sibley, and R. J. Lefkowitz, Desensitization of the turkey erythrocyte beta-adrenergic receptor in a cell-free system. Evidence that multiple protein kinases can phosphorylate and desensitize the receptor, J. Biol. Chem, vol.260, pp.2165-2171, 1985.

D. M. Nanus, D. Engelstein, G. A. Gastl, L. Gluck, M. J. Vidal et al., Molecular cloning of the human kidney differentiation antigen gp160: human aminopeptidase A, Proc. Natl. Acad. Sci. U.S.A, vol.90, pp.7069-7073, 1993.

S. Narayanan, R. Maitra, J. R. Deschamps, K. Bortoff, J. B. Thomas et al., Discovery of a novel small molecule agonist scaffold for the APJ receptor, Bioorg. Med. Chem, vol.24, pp.3758-3770, 2016.

R. Natesh, S. L. Schwager, E. D. Sturrock, and K. R. Acharya, Crystal structure of the human angiotensin-converting enzyme-lisinopril complex, Nature, vol.421, pp.551-554, 2003.

S. Nielsen, C. L. Chou, D. Marples, E. I. Christensen, B. K. Kishore et al., Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane, Proc. Natl. Acad. Sci. U.S.A, vol.92, pp.1013-1017, 1995.

M. Nishimura, K. Ohtsuka, M. Sakamoto, A. Nanbu, H. Takahashi et al., Roles of brain angiotensin II and C-type natriuretic peptide in deoxycorticosterone acetatesalt hypertension in rats, J. Hypertens, vol.16, pp.1175-1185, 1998.

F. Noble, G. Banisadr, F. Jardinaud, T. Popovici, R. Lai-kuen et al., First discrete autoradiographic distribution of aminopeptidase N in various structures of rat brain and spinal cord using the selective iodinated inhibitor, Neuroscience, vol.105, pp.479-488, 2001.

S. Nohara, K. Kato, D. Fujiwara, N. Sakuragi, K. Yanagihara et al., Aminopeptidase N (APN/CD13) as a target molecule for scirrhous gastric cancer, Clin Res Hepatol Gastroenterol, vol.40, pp.494-503, 2016.

T. D. Ocain and D. H. Rich, Synthesis of sulfur-containing analogues of bestatin. Inhibition of aminopeptidases by alpha-thiolbestatin analogues, J. Med. Chem, vol.31, pp.2193-2199, 1988.

T. D. Ocain and D. H. Rich, L-lysinethiol: a subnanomolar inhibitor of aminopeptidase B, Biochem. Biophys. Res. Commun, vol.145, pp.1038-1042, 1987.

.. Oocaaaoll and S. J. Lolait, Regulation of rat APJ receptor messenger ribonucleic acid expression in magnocellular neurones of the paraventricular and supraopric nuclei by osmotic stimuli, J. Neuroendocrinol, vol.15, pp.661-666, 2003.

À. Á. Oocaaaoll, T. L. Palkoits, M. Lolait, and &. J. , Disttiutiooà ofà 'Náà eeeodigà B78/apj, the rat homologue of the human APJ receptor, and its endogenous ligand apelin in brain and peripheral tissues, Biochim. Biophys. Acta, vol.1492, pp.72-80

À. F. Oodod, .. H. , .. C. , and .. L. ,

S. R. George and T. Nguyen, A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11, Gene, vol.136, pp.355-360, 1993.

À. Oeffee, .. K. , and .. E. , ttuutuueàofàhuuaaàeuttalà endopeptidase (Neprilysin) complexed with phosphoramidon, J. Mol. Biol, vol.296, pp.341-349

L. D. Ofner and N. M. Hooper, The C-terminal domain, but not the interchain disulphide, is required for the activity and intracellular trafficking of aminopeptidase A, Biochem. J, vol.362, pp.191-197, 2002.

Y. Ogawa, A. Ohnishi, Y. Goto, Y. Sakuma, J. Watanabe et al., Role of glutamine-169 in the substrate recognition of human aminopeptidase B, Biochim. Biophys. Acta, vol.1840, pp.1872-1881, 2014.

A. Ohnishi, J. Watanabe, Y. Ogawa, Y. Goto, A. Hattori et al., Involvement of Phenylalanine 297 in the Construction of the Substrate Pocket of Human Aminopeptidase B, Biochemistry, vol.54, pp.6062-6070, 2015.

K. Okamoto and K. Aoki, Development of a strain of spontaneously hypertensive rats, Jpn. Circ. J, vol.27, pp.282-293, 1963.

T. Okuyama, S. Ishiura, M. Nojima, T. Tsukahara, M. Yanagida et al., Aminopeptidase A in human placenta and pregnant serum, Clin. Chim. Acta, vol.196, pp.207-215, 1991.

W. M. Oldham and H. E. Hamm, Heterotrimeric G protein activation by G-protein-coupled receptors, Nat. Rev. Mol. Cell Biol, vol.9, pp.60-71, 2008.

W. D. Ollis and A. J. East, Presented at the I.A.M symposia on microbiology. Chemistry of microbial product. The microbial research foundation, 1964.

J. Olsen, G. M. Cowell, E. Kønigshøfer, E. M. Danielsen, J. Møller et al., Complete amino acid sequence of human intestinal aminopeptidase N as deduced from cloned cDNA, FEBS Lett, vol.238, pp.307-314, 1988.

C. K. Olson and F. Binkley, Metabolism of glutathione. III. Enzymatic hydrolysis of cysteinylglycine, J. Biol. Chem, vol.186, pp.731-735, 1950.

S. Oparil, Renin inhibitors in the management of hypertension, J Clin Hypertens (Greenwich), vol.9, pp.706-707, 2007.

À. L. Osttooski, &. J. , .. J. , .. M. , and .. J. , ,à.à Distribution of V1a and V2 vasopressin receptor messenger ribonucleic acids in rat liver, kidney, pituitary and brain, Endocrinology, vol.131, pp.533-535

K. Palin, M. L. Moreau, H. Orcel, A. Duvoid-guillou, A. Rabié et al., Age-impaired fluid homeostasis depends on the balance of IL-6/IGF-I in the rat supraoptic nuclei, Neurobiol. Aging, vol.30, pp.1677-1692, 2009.

K. Palin, M. L. Moreau, J. Sauvant, H. Orcel, A. Nadjar et al., Interleukin-6 activates arginine vasopressin neurons in the supraoptic nucleus during immune challenge in rats, Am. J. Physiol. Endocrinol. Metab, vol.296, pp.1289-1299, 2009.

F. E. Palmieri, H. H. Bausback, and P. E. Ward, Metabolism of vasoactive peptides by vascular endothelium and smooth muscle aminopeptidase M, Biochem. Pharmacol, vol.38, pp.173-180, 1989.

W. M. Pardridge, Blood-brain barrier delivery, Drug Discov. Today, vol.12, pp.54-61, 2007.

R. Pasqualini, E. Koivunen, and E. Ruoslahti, A peptide isolated from phage display libraries is a structural and functional mimic of an RGD-binding site on integrins, J. Cell Biol, vol.130, pp.1189-1196, 1995.

M. Paul, M. P. Printz, E. Harms, T. Unger, R. E. Lang et al., Localization of renin (EC 3.4.23) and converting enzyme (EC in nerve endings of rat brain, Brain Res, vol.334, pp.315-324, 1985.

Y. A. Pelogeykina, G. G. Konovalova, O. I. Pisarenko, and V. Z. Lankin, Antioxidant Action of Apelin-12 Peptide and Its Structural Analog In Vitro, Bull. Exp. Biol. Med, vol.159, pp.604-606, 2015.

À. &. Pettooi? and À. L. Vitale, Puuifiatiooà aadà ppopeetiesà ofà glutaaalà aaiopeptidaseà ffooà chicken egg-white, Comp. Biochem. Physiol., B, vol.95, pp.589-595

V. Pham, à ááiopeptidaseà B :à oddlisatiooà olulaieà età tudeà duà siteà aatifà paaà mutagenèse dirigée

V. Pham, M. Cadel, C. Gouzy-darmon, C. Hanquez, M. C. Beinfeld et al., Aminopeptidase B, a glucagon-processing enzyme: site directed mutagenesis of the Zn2+-binding motif and molecular modelling, BMC Biochem, vol.8, p.21, 2007.

V. Pham, C. Gouzy-darmon, J. Pernier, C. Hanquez, V. Hook et al., Mutation in the substrate-binding site of aminopeptidase B confers new enzymatic properties, Biochimie, vol.93, pp.730-741, 2011.

M. I. Phillips, Functions of angiotensin in the central nervous system, Annu. Rev. Physiol, vol.49, pp.413-435, 1987.

M. I. Phillips and B. Kimura, Brain angiotensin in the developing spontaneously hypertensive rat, J. Hypertens, vol.6, pp.607-612, 1988.

P. A. Phillips, B. J. Rolls, J. G. Ledingham, M. L. Forsling, J. J. Morton et al., Reduced thirst after water deprivation in healthy elderly men, N. Engl. J. Med, vol.311, pp.753-759, 1984.

V. M. Pickel, J. Chan, and D. Ganten, Dual peroxidase and colloidal gold-labeling study of angiotensin converting enzyme and angiotensin-like immunoreactivity in the rat subfornical organ, J. Neurosci, vol.6, pp.2457-2469, 1986.

C. Piesse, M. Tymms, E. Garrafa, C. Gouzy, M. Lacasa et al., Human aminopeptidase B (rnpep) on chromosome 1q32.2: complementary DNA, genomic structure and expression, Gene, vol.292, pp.129-140, 2002.

O. I. Pisarenko, V. S. Shulzhenko, Y. A. Pelogeykina, and I. M. Studneva, Enhancement of crystalloid cardioplegic protection by structural analogs of apelin-12, J. Surg. Res, vol.194, pp.18-24, 2015.

G. R. Pope, E. M. Roberts, and S. J. Lolait, Central and peripheral apelin receptor distribution in the mouse: species differences with rat, Peptides, vol.33, pp.139-148, 2012.

D. A. Poulain, J. B. Wakerley, and R. E. Dyball, Electrophysiological differentiation of oxytocin-and vasopressin-secreting neurones, Proc. R. Soc. Lond., B, Biol. Sci, vol.196, pp.367-384, 1977.

A. M. Preininger and H. E. Hamm, G protein signaling: insights from new structures, 2004.
DOI : 10.1126/stke.2182004re3

, STKE 2004, re3

A. M. Preininger, N. Van-eps, N. Yu, M. Medkova, W. L. Hubbell et al., The myristoylated amino terminus of Galpha(i)(1) plays a critical role in the structure and function of Galpha(i)(1) subunits in solution, Biochemistry, vol.42, pp.7931-7941, 2003.

R. T. Premont and R. R. Gainetdinov, Physiological roles of G protein-coupled receptor kinases and arrestins, Annu. Rev. Physiol, vol.69, pp.511-534, 2007.

M. K. Raizada, D. Lu, W. Tang, P. Kurian, and C. Sumners, Increased angiotensin II type-1 receptor gene expression in neuronal cultures from spontaneously hypertensive rats, Endocrinology, vol.132, pp.1715-1722, 1993.
DOI : 10.1210/en.132.4.1715

S. G. Rasmussen, H. Choi, D. M. Rosenbaum, T. S. Kobilka, F. S. Thian et al., Crystal structure of the human beta2 adrenergic G-protein-coupled receptor, Nature, vol.450, pp.383-387, 2007.

S. G. Rasmussen, B. T. Devree, Y. Zou, A. C. Kruse, K. Y. Chung et al., Crystal structure of the ?2 adrenergic receptor-Gs protein complex, Nature, vol.477, pp.549-555, 2011.

R. Rastaldo, S. Cappello, A. Folino, and G. Losano, Effect of apelin-apelin receptor system in postischaemic myocardial protection: a pharmacological postconditioning tool?, Antioxid. Redox Signal, vol.14, pp.909-922, 2011.

N. D. Rawlings and A. J. Barrett, Evolutionary families of metallopeptidases, Meth. Enzymol, vol.248, pp.183-228, 1995.

N. D. Rawlings and A. J. Barrett, Evolutionary families of peptidases, Biochem. J, vol.290, pp.205-218, 1993.
DOI : 10.1042/bj2900205

URL : http://europepmc.org/articles/pmc1132403?pdf=render

K. Ray, C. S. Hines, J. Coll-rodriguez, and D. W. Rodgers, Crystal structure of human thimet oligopeptidase provides insight into substrate recognition, regulation, and localization, J. Biol. Chem, vol.279, pp.20480-20489, 2004.

C. Read, C. M. Fitzpatrick, P. Yang, R. E. Kuc, J. J. Maguire et al., Cardiac action of the first G protein biased small molecule apelin agonist, Biochem. Pharmacol, vol.116, pp.63-72, 2016.

A. Reaux, N. De-mota, I. Skultetyova, Z. Lenkei, S. El-messari et al., Physiological role of a novel neuropeptide, apelin, and its receptor in the rat brain, J. Neurochem, vol.77, pp.1085-1096, 2001.

A. Réaux, N. De-mota, S. Zini, S. Cadel, M. C. Fournié-zaluski et al., PC18, a specific aminopeptidase N inhibitor, induces vasopressin release by increasing the half-life of brain angiotensin III, Neuroendocrinology, vol.69, p.54439, 1999.

A. Reaux, M. C. Fournie-zaluski, C. David, S. Zini, B. P. Roques et al., Aminopeptidase A inhibitors as potential central antihypertensive agents, Proc. Natl. Acad. Sci. U.S.A, vol.96, pp.13415-13420, 1999.
DOI : 10.1073/pnas.96.23.13415

URL : http://europepmc.org/articles/pmc23962?pdf=render

A. Reaux, K. Gallatz, M. Palkovits, and C. Llorens-cortes, Distribution of apelin-synthesizing neurons in the adult rat brain, Neuroscience, vol.113, pp.653-662, 2002.

R. Goazigo, A. Morinville, A. Burlet, A. Llorens-cortes, C. Beaudet et al., Dehydration-induced cross-regulation of apelin and vasopressin immunoreactivity levels in magnocellular hypothalamic neurons, Endocrinology, vol.145, pp.4392-4400, 2004.

D. Reverter, K. Maskos, F. Tan, R. A. Skidgel, and W. Bode, Crystal structure of human carboxypeptidase M, a membrane-bound enzyme that regulates peptide hormone activity, J. Mol. Biol, vol.338, pp.257-269, 2004.

J. P. Richoux, J. Bouhnik, E. Clauser, and P. Corvol, The renin-angiotensin system in the rat brain. Immunocytochemical localization of angiotensinogen in glial cells and neurons, Histochemistry, vol.89, pp.323-331, 1988.

M. A. Robien, K. T. Nguyen, A. Kumar, I. Hirsh, S. Turley et al., An improved crystal form of Plasmodium falciparum peptide deformylase, Protein Sci, vol.13, pp.1155-1163, 2004.
DOI : 10.1110/ps.03456404

URL : https://onlinelibrary.wiley.com/doi/pdf/10.1110/ps.03456404

L. M. Roman and A. L. Hubbard, A domain-specific marker for the hepatocyte plasma membrane. II. Ultrastructural localization of leucine aminopeptidase to the bile canalicular domain of isolated rat liver plasma membranes, J. Cell Biol, vol.98, pp.1488-1496, 1984.

L. M. Roman and A. L. Hubbard, A domain-specific marker for the hepatocyte plasma membrane. III. Isolation of bile canalicular membrane by immunoadsorption, J. Cell Biol, vol.98, pp.1497-1504, 1984.

G. Ronquist, Zinc ion stimulation of ATP cleavage by prostasomes from human seminal plasma, Urol. Int, vol.43, pp.334-340, 1988.

B. P. Roques and M. C. Fournie-zaluski, Enkephalin degrading enzyme inhibitors: a physiological way to new analgesics and psychoactive agents, NIDA Res. Monogr, vol.70, pp.128-154, 1986.
DOI : 10.1037/e496782006-008

E. M. Ross and A. G. Gilman, Reconstitution of catecholamine-sensitive adenylate cyclase activity: interactions of solubilized components with receptor-replete membranes, Proc. Natl. Acad. Sci. U.S.A, vol.74, pp.3715-3719, 1977.

R. Rozenfeld, X. Iturrioz, B. Maigret, and C. Llorens-cortes, Contribution of molecular modeling and site-directed mutagenesis to the identification of two structural residues, Arg220 and Asp-227, in aminopeptidase A, J. Biol. Chem, vol.277, pp.29242-29252, 2002.

R. Rozenfeld, X. Iturrioz, M. Okada, B. Maigret, and C. Llorens-cortes, Contribution of molecular modeling and site-directed mutagenesis to the identification of a new residue, glutamate 215, involved in the exopeptidase specificity of aminopeptidase A, Biochemistry, vol.42, pp.14785-14793, 2003.

R. Rozenfeld, L. Muller, S. El-messari, and C. Llorens-cortes, The C-terminal domain of aminopeptidase A is an intramolecular chaperone required for the correct folding, cell surface expression, and activity of this monozinc aminopeptidase, J. Biol. Chem, vol.279, pp.43285-43295, 2004.
URL : https://hal.archives-ouvertes.fr/hal-02125635

P. C. Rudberg, F. Tholander, M. M. Thunnissen, and J. Z. Haeggström, Leukotriene A4 hydrolase/aminopeptidase. Glutamate 271 is a catalytic residue with specific roles in two distinct enzyme mechanisms, J. Biol. Chem, vol.277, pp.1398-1404, 2002.

M. C. Ryan, P. J. Shen, and A. L. Gundlach, Angiotensinogen and natriuretic peptide mRNAs in rat brain: localization and differential regulation by adrenal steroids in hypothalamus, Peptides, vol.18, pp.495-504, 1997.

J. M. Saavedra, Brain and pituitary angiotensin, Endocr. Rev, vol.13, pp.329-380, 1992.
DOI : 10.1210/er.13.2.329

A. Salcedo, J. Garijo, L. Monge, N. Fernández, L. García-villalón et al., Apelin effects in human splanchnic arteries. Role of nitric oxide and prostanoids, Regul. Pept, vol.144, pp.50-55, 2007.

J. M. Sands, M. Naruse, M. Baum, I. Jo, S. C. Hebert et al., Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct, J. Clin. Invest, vol.99, pp.1399-1405, 1997.

A. Santoro, L. Rimassa, A. F. Sobrero, G. Citterio, F. Sclafani et al., Phase II study of NGR-hTNF, a selective vascular targeting agent, in patients with metastatic colorectal cancer after failure of standard therapy, Eur. J. Cancer, vol.46, pp.2746-2752, 2010.

B. Sanz, I. Perez, M. Beitia, P. Errarte, A. Fernández et al., Aminopeptidase N activity predicts 5-year survival in colorectal cancer patients, J. Investig. Med, vol.63, pp.740-746, 2015.

J. Sauvant, J. Delpech, K. Palin, N. De-mota, J. Dudit et al., Mechanisms involved in dual vasopressin/apelin neuron dysfunction during aging, PLoS ONE, vol.9, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01369526

P. Schelling, D. Meyer, H. E. Loos, G. Speck, M. I. Phillips et al., A micromethod for the measurement of renin in brain nuclei: its application in spontaneously hypertensive rats, Neuropharmacology, vol.21, pp.455-463, 1982.

J. E. Scherberich, J. Wiemer, C. Herzig, P. Fischer, and W. Schoeppe, Isolation and partial characterization of angiotensinase A and aminopeptidase M from urine and human kidney by lectin affinity chromatography and high-performance liquid chromatography, J. Chromatogr, vol.521, pp.279-289, 1990.

H. B. Schiöth and R. Fredriksson, The GRAFS classification system of G-protein coupled receptors in comparative perspective, Gen. Comp. Endocrinol, vol.142, pp.94-101, 2005.

C. J. Schmidt, T. C. Thomas, M. A. Levine, and E. J. Neer, Specificity of G protein beta and gamma subunit interactions, J. Biol. Chem, vol.267, pp.13807-13810, 1992.

R. Schnabel, H. G. Bernstein, H. Luppa, Z. Lojda, and A. Barth, Aminopeptidases in the circumventricular organs of the mouse brain: a histochemical study, Neuroscience, vol.47, pp.431-438, 1992.

H. Schulz, G. E. Dale, Y. Karimi-nejad, and C. Oefner, Structure of human endothelinconverting enzyme I complexed with phosphoramidon, J. Mol. Biol, vol.385, pp.178-187, 2009.

V. Serpooshan, S. Sivanesan, X. Huang, M. Mahmoudi, A. V. Malkovskiy et al., Apelin-13 delivery via nano-liposomal encapsulation attenuates pressure overload-induced cardiac dysfunction, Biomaterials, vol.37, pp.289-298, 2015.
DOI : 10.1016/j.biomaterials.2014.08.045

URL : http://europepmc.org/articles/pmc5555682?pdf=render

M. Seyedabadi, A. K. Goodchild, and P. M. Pilowsky, Site-specific effects of apelin-13 in the rat medulla oblongata on arterial pressure and respiration, Auton Neurosci, vol.101, pp.32-38, 2002.

S. K. Shenoy and R. J. Lefkowitz, Multifaceted roles of beta-arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling, Biochem. J, vol.375, pp.503-515, 2003.

L. Shi and J. A. Javitch, The second extracellular loop of the dopamine D2 receptor lines the binding-site crevice, Proc. Natl. Acad. Sci. U.S.A, vol.101, pp.440-445, 2004.

K. Shimada, M. Takahashi, A. J. Turner, and K. Tanzawa, Rat endothelin-converting enzyme-1 forms a dimer through Cys412 with a similar catalytic mechanism and a distinct substrate binding mechanism compared with neutral endopeptidase-24.11, Biochem. J, vol.315, pp.863-867, 1996.

M. Shimamura, T. Hazato, M. Hachisu, and T. Katayama, Inhibition of a membrane-bound enkephalin-degrading aminopeptidase by bestatin analogs, J. Neurochem, vol.43, pp.888-890, 1984.

T. Shimizu, O. Rådmark, and B. Samuelsson, Enzyme with dual lipoxygenase activities catalyzes leukotriene A4 synthesis from arachidonic acid, Proc. Natl. Acad. Sci. U.S.A, vol.81, pp.689-693, 1984.
DOI : 10.1073/pnas.81.3.689

URL : http://www.pnas.org/content/81/3/689.full.pdf

K. Shin, A. Pandey, X. Liu, Y. Anini, and J. K. Rainey, Preferential apelin-13 production by the proprotein convertase PCSK3 is implicated in obesity, FEBS Open Bio, vol.3, pp.328-333, 2013.

A. K. Shukla, A. Manglik, A. C. Kruse, K. Xiao, R. I. Reis et al., Structure of active ?-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide, Nature, vol.497, pp.137-141, 2013.

D. A. Sica, Hyponatremia and heart failure-pathophysiology and implications, Congest Heart Fail, vol.11, pp.274-277, 2005.
DOI : 10.1111/j.1527-5299.2005.04180.x

K. Siddiquee, J. Hampton, D. Mcanally, L. May, and L. Smith, The apelin receptor inhibits the angiotensin II type 1 receptor via allosteric trans-inhibition, .x "idooooa,àM.V.,àázzzuko,àá.á.,àPalkeeea, vol.168, pp.1104-1117, 2013.

, Bioorg. Khim, vol.38, pp.40-51

N. R. Silvaggi, J. W. Anderson, S. R. Brinsmade, R. F. Pratt, and J. A. Kelly, The crystal structure of phosphonate-inhibited D-Ala-D-Ala peptidase reveals an analogue of a tetrahedral transition state, Biochemistry, vol.42, pp.1199-1208, 2003.

M. I. Simon, M. P. Strathmann, and N. Gautam, Diversity of G proteins in signal transduction, Science, vol.252, pp.802-808, 1991.

F. Y. Siu, M. He, C. De-graaf, G. W. Han, D. Yang et al., Structure of the human glucagon class B G-protein-coupled receptor, Nature, vol.499, pp.444-449, 2013.

C. D. Sladek and J. A. Olschowka, Dehydration induces Fos, but not increased vasopressin mRNA in the supraoptic nucleus of aged rats, Brain Res, vol.652, pp.207-215, 1994.

E. E. Slater, R. Defendini, and E. A. Zimmerman, Wide distribution of immunoreactive renin in nerve cells of human brain, Proc. Natl. Acad. Sci. U.S.A, vol.77, pp.5458-5460, 1980.

B. Solhonne, C. Gros, H. Pollard, and J. C. Schwartz, Major localization of aminopeptidase M in rat brain microvessels, Neuroscience, vol.22, pp.225-232, 1987.

J. Sondek, A. Bohm, D. G. Lambright, H. E. Hamm, and P. B. Sigler, Crystal structure of a Gprotein beta gamma dimer at 2.1A resolution, Nature, vol.379, pp.369-374, 1996.

K. Song, Y. Kurobe, H. Kanehara, H. Okunishi, T. Wada et al., Quantitative localization of angiotensin II receptor subtypes in spontaneously hypertensive rats, Blood Press Suppl, vol.5, pp.21-26, 1994.

L. Song, E. Wilk, S. Wilk, and D. P. Healy, Localization of immunoreactive glutamyl aminopeptidase in rat brain. I. Association with cerebral microvessels, Brain Res, vol.606, pp.286-294, 1993.

L. Song, S. Wilk, and D. P. Healy, Aminopeptidase A antiserum inhibits intracerebroventricular angiotensin II-induced dipsogenic and pressor responses, Brain Res, vol.744, pp.1-6, 1997.
DOI : 10.1016/s0006-8993(96)00952-3

L. Song, M. Ye, M. Troyanovskaya, E. Wilk, S. Wilk et al., Rat kidney glutamyl aminopeptidase (aminopeptidase A): molecular identity and cellular localization, Am. J. Physiol, vol.267, pp.546-557, 1994.
DOI : 10.1152/ajprenal.1994.267.4.f546

D. Spengler, C. Waeber, C. Pantaloni, F. Holsboer, J. Bockaert et al., Differential signal transduction by five splice variants of the PACAP receptor, Nature, vol.365, pp.170-175, 1993.

V. Stefanovic, P. Vlahovic, N. Ardaillou, and R. Ardaillou, Receptor-mediated induction of aminopeptidase A (APA) of human glomerular epithelial cells (HGEC) by glucocorticoids, FEBS Lett, vol.294, pp.171-174, 1991.

R. L. Stornetta, C. L. Hawelu-johnson, P. G. Guyenet, and K. R. Lynch, Astrocytes synthesize angiotensinogen in brain, Science, vol.242, pp.1444-1446, 1988.
DOI : 10.1126/science.3201232

B. Stragier, H. Demaegdt, D. De-bundel, I. Smolders, S. Sarre et al., Involvement of insulin-regulated aminopeptidase and/or aminopeptidase N in the angiotensin IV-induced effect on dopamine release in the striatum of the rat, Brain Res, vol.1131, pp.97-105, 2007.

M. P. Strathmann and M. I. Simon, G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits, Proc. Natl. Acad. Sci. U.S.A, vol.88, pp.5582-5586, 1991.

S. M. Strittmatter, M. M. Lo, J. A. Javitch, and S. H. Snyder, Autoradiographic visualization of angiotensin-converting enzyme in rat brain with [3H]captopril: localization to a striatonigral pathway, Proc. Natl. Acad. Sci. U.S.A, vol.81, pp.1599-1603, 1984.

B. Sun, P. Bachhawat, M. L. Chu, M. Wood, T. Ceska et al., Crystal structure of the adenosine A2A receptor bound to an antagonist reveals a potential allosteric pocket, Proc. Natl. Acad. Sci. U.S.A, 2017.

X. Sun, S. Iida, A. Yoshikawa, R. Senbonmatsu, K. Imanaka et al., Non-activated APJ suppresses the angiotensin II type 1 receptor, whereas apelin-activated APJ acts conversely, Hypertens. Res, vol.34, pp.701-706, 2011.
DOI : 10.1038/hr.2011.19

URL : https://www.nature.com/articles/hr201119.pdf

P. Surendran, F. Drenos, R. Young, H. Warren, J. P. Cook et al.,

D. F. Freitag, T. Ferreira, O. Giannakopoulou, A. Tinker, M. Harakalova et al., CHARGE-Heart Failure Consortium, Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension, vol.48, pp.1151-1161, 2016.

N. Suzuki, N. Hajicek, and T. Kozasa, Regulation and physiological functions of G12/13mediated signaling pathways, Neurosignals, vol.17, pp.55-70, 2009.

I. Szokodi, P. Tavi, G. Földes, S. Voutilainen-myllylä, M. Ilves et al., Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility, Circ. Res, vol.91, pp.434-440, 2002.

K. Tatemoto, M. Hosoya, Y. Habata, R. Fujii, T. Kakegawa et al., Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor, Biochem. Biophys. Res. Commun, vol.251, pp.471-476, 1998.

K. Tatemoto, K. Takayama, M. X. Zou, I. Kumaki, W. Zhang et al., The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism, Regul. Pept, vol.99, pp.87-92, 2001.

D. Terwel, J. A. Ten-haaf, M. Markerink, and J. Jolles, Changes in plasma vasopressin concentration and plasma osmolality in relation to age and time of day in the male Wistar rat, Acta Endocrinol, vol.126, pp.357-362, 1992.

A. R. Thomsen, B. Plouffe, T. J. Cahill, A. K. Shukla, J. T. Tarrasch et al., GPCR-G Protein-?-Arrestin Super-Complex Mediates Sustained G Protein Signaling, Cell, vol.166, pp.907-919, 2016.

E. .. Thorsett and M. .. Wyvratt, inhibition of zinc peptidases that hydrolyses neuropeptides, in: Neuropeptides and Their Peptidases, AJ Turner, pp.229-292, 1987.

M. M. Thunnissen, P. Nordlund, and J. Z. Haeggström, Crystal structure of human leukotriene A(4) hydrolase, a bifunctional enzyme in inflammation, Nat. Struct. Biol, vol.8, pp.131-135, 2001.

S. Tieku and N. M. Hooper, Inhibition of aminopeptidases N, A and W. A re-evaluation of the actions of bestatin and inhibitors of angiotensin converting enzyme, Biochem. Pharmacol, vol.44, pp.1725-1730, 1992.

V. I. Timofeev, S. A. Kuznetsov, V. K. Akparov, G. G. Chestukhina, and I. P. Kuranova, Threedimensional structure of carboxypeptidase T from Thermoactinomyces vulgaris in complex with N-BOC-L-leucine, Biochemistry Mosc, vol.78, pp.252-259, 2013.

K. Timper, W. Fenske, F. Kühn, N. Frech, B. Arici et al., Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study, J. Clin. Endocrinol. Metab, vol.100, pp.2268-2274, 2015.

K. Titani, M. A. Hermodson, L. H. Ericsson, K. A. Walsh, and H. Neurath, Amino-acid sequence of thermolysin, Nature New Biol, vol.238, pp.35-37, 1972.

H. Tobe, F. Kojima, T. Aoyagi, and H. Umezawa, Purification by affinity chromatography using amastatin and properties of aminopeptidase A from pig kidney, Biochim. Biophys. Acta, vol.613, pp.459-468, 1980.

M. Tokioka-terao, K. Hiwada, and T. Kokubu, Purification and characterization of aminopeptidase N from human plasma, Enzyme, vol.32, pp.65-75, 1984.

T. Tokuhara, N. Hattori, H. Ishida, T. Hirai, M. Higashiyama et al., Clinical significance of aminopeptidase N in non-small cell lung cancer, Clin. Cancer Res, vol.12, pp.3971-3978, 2006.

S. Tonna, S. V. Dandapani, A. Uscinski, G. B. Appel, J. S. Schlöndorff et al., Functional genetic variation in aminopeptidase A (ENPEP): lack of clear association with focal and segmental glomerulosclerosis (FSGS), Gene, vol.410, pp.44-52, 2008.

P. Towler, B. Staker, S. G. Prasad, S. Menon, J. Tang et al., ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis, J. Biol. Chem, vol.279, pp.17996-18007, 2004.

A. J. Trask, J. A. Jessup, M. C. Chappell, and C. M. Ferrario, Angiotensin-(1-12) is an alternate substrate for angiotensin peptide production in the heart, Am. J. Physiol. Heart Circ. Physiol, vol.294, pp.2242-2247, 2008.

D. E. Tronrud, H. M. Holden, and B. W. Matthews, Structures of two thermolysin-inhibitor complexes that differ by a single hydrogen bond, Science, vol.235, pp.571-574, 1987.

D. E. Tronrud, A. F. Monzingo, and B. W. Matthews, Crystallographic structural analysis of phosphoramidates as inhibitors and transition-state analogs of thermolysin, Eur. J. Biochem, vol.157, pp.261-268, 1986.

M. Troyanovskaya, G. Jayaraman, L. Song, and D. P. Healy, Aminopeptidase-A. I. CDNA cloning and expression and localization in rat tissues, Am. J. Physiol. Regul. Integr. Comp. Physiol, vol.278, pp.413-424, 2000.

H. Uchino, Y. Kanai, D. K. Kim, M. F. Wempe, A. Chairoungdua et al., Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition, Mol. Pharmacol, vol.61, pp.729-737, 2002.

H. Umezawa, Structures and activities of protease inhibitors of microbial origin, Meth. Enzymol, vol.45, pp.678-695, 1976.

C. Urso, S. Brucculeri, and G. Caimi, Acid-base and electrolyte abnormalities in heart failure: pathophysiology and implications, Heart Fail Rev, vol.20, pp.493-503, 2015.
DOI : 10.1007/s10741-015-9482-y

URL : https://link.springer.com/content/pdf/10.1007%2Fs10741-015-9482-y.pdf

S. A. Urwyler, K. Timper, W. Fenske, N. De-mota, A. Blanchard et al., Plasma Apelin Concentrations in Patients With Polyuria-Polydipsia Syndrome, J. Clin. Endocrinol. Metab, vol.101, pp.1917-1923, 2016.
DOI : 10.1210/jc.2016-1158

URL : https://academic.oup.com/jcem/article-pdf/101/5/1917/10427389/jcem1917.pdf

B. L. Vallee and D. S. Auld, Zinc coordination, function, and structure of zinc enzymes and other proteins, Biochemistry, vol.29, pp.5647-5659, 1990.
DOI : 10.1021/bi00476a001

G. Vazeux, X. Iturrioz, P. Corvol, and C. Llorens-cortes, A glutamate residue contributes to the exopeptidase specificity in aminopeptidase A, Biochem. J, vol.334, pp.407-413, 1998.

G. Vazeux, X. Iturrioz, P. Corvol, and C. Llorens-cortès, A tyrosine residue essential for catalytic activity in aminopeptidase A, Biochem. J, vol.327, pp.883-889, 1997.

G. Vazeux, J. Wang, P. Corvol, and C. Llorens-cortès, Identification of glutamate residues essential for catalytic activity and zinc coordination in aminopeptidase A, J. Biol. Chem, vol.271, pp.9069-9074, 1996.

A. J. Venkatakrishnan, X. Deupi, G. Lebon, C. G. Tate, G. F. Schertler et al., Molecular signatures of G-protein-coupled receptors, Nature, vol.494, pp.185-194, 2013.

C. Vickers, P. Hales, V. Kaushik, L. Dick, J. Gavin et al., Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase, J. Biol. Chem, vol.277, pp.14838-14843, 2002.

D. Wacker, S. Wang, J. D. Mccorvy, R. M. Betz, A. J. Venkatakrishnan et al., Crystal Structure of an LSD-Bound Human Serotonin Receptor. Cell, vol.168, pp.377-389, 2017.

C. Wang, J. Du, F. Wu, and H. Wang, Apelin decreases the SR Ca2+ content but enhances the amplitude of [Ca2+]i transient and contractions during twitches in isolated rat cardiac myocytes, Am. J. Physiol. Heart Circ. Physiol, vol.294, pp.2540-2546, 2008.

C. Wang, H. Wu, V. Katritch, G. W. Han, X. Huang et al., Structure of the human smoothened receptor bound to an antitumour agent, Nature, vol.497, pp.338-343, 2013.

J. Wang and M. D. Cooper, Histidine residue in the zinc-binding motif of aminopeptidase A is critical for enzymatic activity, Proc. Natl. Acad. Sci. U.S.A, vol.90, pp.1222-1226, 1993.

J. Wang, H. Walker, Q. Lin, N. Jenkins, N. G. Copeland et al., The mouse BP-1 gene: structure, chromosomal localization, and regulation of expression by type I interferons and interleukin-7, Genomics, vol.33, pp.167-176, 1996.

L. H. Wang, S. Ahmad, I. F. Benter, A. Chow, S. Mizutani et al., Differential processing of substance P and neurokinin A by plasma dipeptidyl(amino)peptidase IV, aminopeptidase M and angiotensin converting enzyme, Peptides, vol.12, pp.1357-1364, 1991.

L. Wang, D. Zhang, J. Zheng, Y. Zhang, Q. Zhang et al., Apelin-13 passes through the ADMA-damaged endothelial barrier and acts on vascular smooth muscle cells, Peptides, vol.32, pp.2436-2443, 2011.
DOI : 10.1016/j.peptides.2011.10.001

W. Wang, S. M. Mckinnie, M. Farhan, M. Paul, T. Mcdonald et al., Angiotensin-Converting Enzyme, vol.2, 2016.

, Metabolizes and Partially Inactivates Pyr-Apelin-13 and Apelin-17: Physiological Effects in the Cardiovascular System, vol.68, pp.365-377

P. E. Ward, I. F. Benter, L. Dick, and S. Wilk, Metabolism of vasoactive peptides by plasma 200 and purified renal aminopeptidase M, Biochem. Pharmacol, vol.40, pp.1725-1732, 1990.
DOI : 10.1016/0006-2952(90)90348-o

J. M. Watermeyer, B. T. Sewell, S. L. Schwager, R. Natesh, H. R. Corradi et al., Structure of testis ACE glycosylation mutants and evidence for conserved domain movement, Biochemistry, vol.45, pp.12654-12663, 2006.

H. Wei, S. Ahn, S. K. Shenoy, S. S. Karnik, L. Hunyady et al., Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2, Proc. Natl. Acad. Sci. U.S.A, vol.100, pp.10782-10787, 2003.

Q. Wei, T. Ran, C. Ma, J. He, D. Xu et al., Crystal Structure and Function of PqqF Protein in the Pyrroloquinoline Quinone Biosynthetic Pathway, J. Biol. Chem, vol.291, pp.15575-15587, 2016.

J. T. Weissman, J. Ma, A. Essex, Y. Gao, and E. S. Burstein, G-protein-coupled receptormediated activation of rap GTPases: characterization of a novel Galphai regulated pathway, Oncogene, vol.23, pp.241-249, 2004.

A. Wetterholm, J. F. Medina, O. Rådmark, R. Shapiro, J. Z. Haeggström et al., Leukotriene A4 hydrolase: abrogation of the peptidase activity by mutation of glutamic acid-296, Proc. Natl. Acad. Sci. U.S.A, vol.89, pp.9141-9145, 1992.

S. E. Whitham, G. Murphy, P. Angel, H. J. Rahmsdorf, B. J. Smith et al., Comparison of human stromelysin and collagenase by cloning and sequence analysis, Biochem. J, vol.240, pp.913-916, 1986.

S. Wilk and L. S. Thurston, Inhibition of angiotensin III formation by thiol derivatives of acidic amino acids, Neuropeptides, vol.16, pp.163-168, 1990.

T. A. Williams, P. Corvol, and F. Soubrier, Identification of two active site residues in human angiotensin I-converting enzyme, J. Biol. Chem, vol.269, pp.29430-29434, 1994.

K. M. Wilson, C. Sumners, S. Hathaway, and M. J. Fregly, Mineralocorticoids modulate central angiotensin II receptors in rats, Brain Res, vol.382, pp.87-96, 1986.

A. H. Wong, D. Zhou, and J. M. Rini, The X-ray crystal structure of human aminopeptidase N reveals a novel dimer and the basis for peptide processing, J. Biol. Chem, vol.287, pp.36804-36813, 2012.

J. W. Wright, H. Z. Amir, C. E. Murray, K. A. Roberts, J. W. Harding et al., Use of aminopeptidase M as a hypotensive agent in spontaneously hypertensive rats, Brain Res. Bull, vol.27, pp.545-551, 1991.

J. W. Wright, L. L. Jensen, K. A. Roberts, M. F. Sardinia, and J. W. Harding, Structure-function analyses of brain angiotensin control of pressor action in rats, Am. J. Physiol, vol.257, pp.1551-1557, 1989.

J. W. Wright, S. Mizutani, C. E. Murray, H. Z. Amir, and J. W. Harding, Aminopeptidaseinduced elevations and reductions in blood pressure in the spontaneously hypertensive rat, J. Hypertens, vol.8, pp.969-974, 1990.

J. W. Wright, S. L. Morseth, R. H. Abhold, and J. W. Harding, Pressor action and dipsogenicity induced by angiotensin II and III in rats, Am. J. Physiol, vol.249, pp.514-521, 1985.

J. W. Wright, K. A. Roberts, V. I. Cook, C. E. Murray, M. F. Sardinia et al., Brain Res, vol.514, pp.5-10, 1990.

J. W. Wright, E. Tamura-myers, W. L. Wilson, B. P. Roques, C. Llorens-cortes et al., Conversion of brain angiotensin II to angiotensin III is critical for pressor response in rats, Am. J. Physiol. Regul. Integr. Comp. Physiol, vol.284, pp.725-733, 2003.

B. Wu, E. Y. Chien, C. D. Mol, G. Fenalti, W. Liu et al., Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists, Science, vol.330, pp.1066-1071, 2010.

Q. Wu, J. M. Lahti, G. M. Air, P. D. Burrows, and M. D. Cooper, Molecular cloning of the murine BP-1/6C3 antigen: a member of the zinc-dependent metallopeptidase family, Proc. Natl. Acad. Sci. U.S.A, vol.87, pp.993-997, 1990.

F. Xie, W. Liu, F. Feng, X. Li, L. He et al., Apelin13 promotes cardiomyocyte hypertrophy via PI3K-Akt-ERK1/2-p70S6K and PI3K-induced autophagy, Acta Biochim. Biophys. Sin. (Shanghai), vol.47, pp.969-980, 2015.

R. Yamada, S. Mizutani, O. Kurauchi, K. Okano, H. Imaizumi et al., Purification and characterization of human placental aminopeptidase A, Enzyme, vol.40, pp.223-230, 1988.

J. Yamauchi, Y. Kaziro, and H. Itoh, Differential regulation of mitogen-activated protein kinase kinase 4 (MKK4) and 7 (MKK7) by signaling from G protein beta gamma subunit in human embryonal kidney 293 cells, J. Biol. Chem, vol.274, pp.1957-1965, 1999.

G. Yang, T. S. Gray, C. D. Sigmund, and M. D. Cassell, The angiotensinogen gene is expressed in both astrocytes and neurons in murine central nervous system, Brain Res, vol.817, pp.123-131, 1999.

H. Y. Yang and N. H. Neff, Distribution and properties of angiotensin converting enzyme of rat brain, J. Neurochem, vol.19, pp.2443-2450, 1972.

Y. Yang, C. Liu, Y. Lin, and F. Li, Structural insights into central hypertension regulation by human aminopeptidase A, J. Biol. Chem, vol.288, pp.25638-25645, 2013.

S. Yasothornsrikul, T. Toneff, S. R. Hwang, and V. Y. Hook, Arginine and lysine aminopeptidase activities in chromaffin granules of bovine adrenal medulla: relevance to prohormone processing, J. Neurochem, vol.70, pp.153-163, 1998.

B. G. Yongue, J. A. Angulo, B. S. Mcewen, and M. M. Myers, Brain and liver angiotensinogen messenger RNA in genetic hypertensive and normotensive rats, Hypertension, vol.17, pp.485-491, 1991.

S. Yoshida, Y. Nakamura, H. Naganawa, T. Aoyagi, and T. Takeuchi, Probestin, a new inhibitor of aminopeptidase M, produced by Streptomyces azureus MH663-2F6. II. Structure 202 determination of probestin, J. Antibiot, vol.43, pp.149-153, 1990.

D. Zhang, Q. Zhao, and B. Wu, Structural Studies of G Protein-Coupled Receptors, Mol. Cells, vol.38, pp.836-842, 2015.

F. Zhang, H. Sun, X. Xiong, Q. Chen, Y. Li et al., Apelin-13 and APJ in paraventricular nucleus contribute to hypertension via sympathetic activation and vasopressin release in spontaneously hypertensive rats, Acta Physiol (Oxf), vol.212, pp.17-27, 2014.

Q. Zhang, J. Wang, H. Zhang, D. Zhao, Z. Zhang et al., Expression and clinical significance of aminopeptidase N/CD13 in non-small cell lung cancer, J Cancer Res Ther, vol.11, pp.223-228, 2015.

H. Zhong and R. R. Neubig, Regulator of G protein signaling proteins: novel multifunctional drug targets, J. Pharmacol. Exp. Ther, vol.297, pp.837-845, 2001.

J. Zhong, X. Yu, Y. Huang, L. Yung, C. Lau et al., Apelin modulates aortic vascular tone via endothelial nitric oxide synthase phosphorylation pathway in diabetic mice, Cardiovasc. Res, vol.74, pp.388-395, 2007.

N. Zhou, X. Fan, M. Mukhtar, J. Fang, C. A. Patel et al., Cellcell fusion and internalization of the CNS-based, HIV-1 co-receptor, APJ. Virology, vol.307, pp.22-36, 2003.

N. Zhou, X. Zhang, X. Fan, E. Argyris, J. Fang et al., The N-terminal domain of APJ, a CNS-based coreceptor for HIV-1, is essential for its receptor function and coreceptor activity, Virology, vol.317, pp.84-94, 2003.

J. Zhuo, I. Moeller, T. Jenkins, S. Y. Chai, A. M. Allen et al., Mapping tissue angiotensin-converting enzyme and angiotensin AT1, AT2 and AT4 receptors, J. Hypertens, vol.16, pp.2027-2037, 1998.

H. H. Zingg, D. Lefebvre, and G. Almazan, Regulation of vasopressin gene expression in rat hypothalamic neurons. Response to osmotic stimulation, J. Biol. Chem, vol.261, pp.12956-12959, 1986.

S. Zini, M. C. Fournie-zaluski, E. Chauvel, B. P. Roques, P. Corvol et al., Identification of metabolic pathways of brain angiotensin II and III using specific aminopeptidase inhibitors: predominant role of angiotensin III in the control of vasopressin release, Proc. Natl. Acad. Sci. U.S.A, vol.93, pp.11968-11973, 1996.

S. Zini, P. Masdehors, Z. Lenkei, M. C. Fournie-zaluski, B. P. Roques et al., Aminopeptidase A: distribution in rat brain nuclei and increased activity in spontaneously hypertensive rats, Neuroscience, vol.78, pp.1187-1193, 1997.