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"Utilisation de sondes pyréniques in vivo pour caractériser l'état de phase global de la membrane plasmique de cellules eurcaryotes". Application à la détection de la liaison d'agonistes au recepteur et opioide murin.

Abstract : The development of tools for the screening of new receptors' agonists is a major issue for pharmaceutical research. Currently, the main targets used are the G-protein coupled receptor of the plasma membrane which the activation trigger the signaling pathways involved in many cell functions. The goal of this thesis is the detection, using a spectrofluorometry approach in vivo, of the signaling pathway ignition by the mouse delta opioid receptor (mDOR). DOR is assumed to generate a relocalisation of some lipids (cholesterol) while agonist binding leading to the formation of a liquidordered phase (lo). Thus two fluorescent probes have been synthesized, which the 3beta-hydroxypregn- 5-ene-21-(1-methylpyrenyl)-20-methylidene. Data from calorimetry and RMN-2H studies show that this probe induces the same lipid membranes disturbance than cholesterol. Absorption data of the probe allowed the assessment of a self-association process of cholesterol in model membranes, which is as a function of the acyl-chains saturation degree of phospholipids. Then the polarity sensitive property of the probe has been used to distinguish between ld and lo phases in model membranes. Finally, we incorporated the probes in CHO cells over-expressing mDOR to monitor, by fluorescence spectroscopy, the mean phase state change of the plasma membrane triggered by a mDOR agonist. This is the first step of a new screening approach.
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https://tel.archives-ouvertes.fr/tel-00195744
Contributor : Marie-Josée Pedussault <>
Submitted on : Tuesday, December 11, 2007 - 2:14:30 PM
Last modification on : Friday, January 10, 2020 - 9:08:20 PM
Long-term archiving on: : Friday, November 25, 2016 - 8:25:03 PM

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  • HAL Id : tel-00195744, version 1

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Laurent Le Guyader. "Utilisation de sondes pyréniques in vivo pour caractériser l'état de phase global de la membrane plasmique de cellules eurcaryotes". Application à la détection de la liaison d'agonistes au recepteur et opioide murin.. Autre. Université Paul Sabatier - Toulouse III, 2007. Français. ⟨tel-00195744⟩

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