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Analyse électrophysiologique, pharmacologique et moléculaire de facteurs modulant les effets d'un insecticide, le fipronil, sur des récepteurs gabaergiques d'insectes

Abstract : Ionotropic GABA receptors (GABARs) are inhibited by insecticides such as phenylpyrazoles (fipronil). Two factors that might alter their sensitivity to fipronil were examined: 1) mRNA editing of a GABAR subunit, RDL and 2) PKC phosphorylation. Drosophila RDL subunit presents mutations (A301êS/G or T350êM) that result in insecticide resistance, as well as an editing site (R122êG) in the N-terminal domain. Functional effects of the R122êG editing were assessed by expressing several isoforms of the RDL subunit (mutated or not, edited or not) in Xenopus oocytes. The results show that R122êG editing leads to a decrease of RDL receptors to both GABA and fipronil. Two GABARs subtypes (GABAR1 and GABAR2) are expressed at the surface of Periplaneta americana isolated DUM neurons, GABAR2 being positively modulated by the CaMKII. This cellular model has been used to study, by the patch-clamp technique, GABARs regulation by PKC and its consequences on fipronil effects. GABAR2 appear to be more sensitive to PKC inhibition than GABAR1, and CaMKII potentiation occurs through PKC inhibition. GABAR2 being more sensitive to fipronil than GABAR1, its selective blockade by PKC induces an important decrease in the inhibition exerted by fipronil. The cloning of the RDL subunit in Periplaneta americana nerve cord and in DUM neurons reveals the presence of potential phosphorylation sites by PKC and CaMKII, as well as the existence of two RDL variants that differ by a twenty residues insertion in the M3-M4 loop.
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https://tel.archives-ouvertes.fr/tel-00439681
Contributor : Anne-Marie Plé <>
Submitted on : Monday, January 25, 2010 - 2:42:43 PM
Last modification on : Saturday, May 2, 2020 - 6:14:02 PM
Long-term archiving on: : Thursday, September 23, 2010 - 11:13:04 AM

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  • HAL Id : tel-00439681, version 2

Citation

Zeineb Es-Salah. Analyse électrophysiologique, pharmacologique et moléculaire de facteurs modulant les effets d'un insecticide, le fipronil, sur des récepteurs gabaergiques d'insectes. Interactions entre organismes. Université d'Angers, 2008. Français. ⟨tel-00439681v2⟩

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