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Analyse comparée des récepteurs D1 de la dopamine chez les vertébrés : Définition des caractères fonctionnels spécifiques de chacun des sous-types du récepteur D1

Abstract : Dopamine effect is transmitted by its fixation on receptors that belong to two classes D1 and D2. Four D1 receptor subtypes (D1A, D1B/D5, D1C and D1D) were cloned until today in vertebrates. Evolutive analysis shows that D1A and D1B subtypes are the most conserved while D1C and D1D subtypes are missing in mammals. Despite this diversity, dopamine function in the whole organism cannot be assigned to one specific subtype action. For this reason, all along this work we have identified functional characters which may discriminate each of the subtypes and which help to understand why they were conserved in vertebrates. Desensitisation is one of the most important functional parameter of receptor cell biology. The D1A receptor desensitisation is characterised by a strong and biphasic decrease in activity. The D1B receptor exhibit a similar profile with a weaker amplitude due to its constitutive activity. The D1C receptor does not undergo any desensitisation. Construction of chimerical proteins between each of the D1 receptor subtypes and the GFP fluorescent protein allowed us to visualised the receptor during the desensitisation process. It shows that internalisation, of the D1 dopamine receptor does not occur in conjonction with the general process of desensitisation. These phenomenon are blurred by interaction with the A1 adenosine receptor. To conclude, the analysis of MAPK signalisation pathways show that ERK activation was fast and strong and differentiate each subtypes of the subtypes. Moreover, if the p38 pathway was only weakly activated, the JNK one does not show any activity. Thus, it appears so that differential activation and regulation of signalisation pathway discriminate D1 dopamine receptor subtypes in vertebrates. These parameters participate to the regulated transmission of dopamine functions in the whole organism.
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https://tel.archives-ouvertes.fr/tel-00009188
Contributor : Stéphane Le Crom <>
Submitted on : Thursday, May 5, 2005 - 9:28:06 AM
Last modification on : Thursday, August 27, 2020 - 9:58:37 AM
Long-term archiving on: : Friday, April 2, 2010 - 9:56:35 PM

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  • HAL Id : tel-00009188, version 1

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Stéphane Le Crom. Analyse comparée des récepteurs D1 de la dopamine chez les vertébrés : Définition des caractères fonctionnels spécifiques de chacun des sous-types du récepteur D1. Biologie cellulaire. Université Paris Sud - Paris XI, 2000. Français. ⟨tel-00009188⟩

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