Identification and pharmacological properties of E339-3D6, the first nonpeptidic apelin receptor agonist

Abstract : Apelin plays a prominent role in body fluid and cardiovascular homeostasis. To explore further upstream the role played by this peptide, nonpeptidic agonists and antagonists of the apelin receptor are required. To identify such compounds that do not exist to date, we used an original fluorescence resonance energy transfer-based assay to screen a G-protein-coupled receptor-focused library of fluorescent compounds on the human EGFP-tagged apelin receptor. This led to isolated E339-3D6 that displayed a 90 nM affinity and behaved as a partial agonist with regard to cAMP production and as a full agonist with regard to apelin receptor internalization. Finally, E339-3D6 induced vasorelaxation of rat aorta precontracted with noradrenaline and potently inhibited systemic vasopressin release in water-deprived mice when intracerebroventricularly injected. This compound represents the first nonpeptidic agonist of the apelin receptor, the optimization of which will allow development of a new generation of vasodilator and aquaretic agents.
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https://hal.archives-ouvertes.fr/hal-00547967
Contributor : Bernard Maigret <>
Submitted on : Saturday, December 18, 2010 - 1:10:25 AM
Last modification on : Friday, October 4, 2019 - 1:36:11 AM

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  • HAL Id : hal-00547967, version 1
  • PUBMED : 20040517

Citation

Xavier Iturrioz, Rodrigo Alvear-Perez, Nadia de Mota, Christel Franchet, Fabrice Guillier, et al.. Identification and pharmacological properties of E339-3D6, the first nonpeptidic apelin receptor agonist. FASEB Journal, Federation of American Society of Experimental Biology, 2010, 24 (5), pp.1506-1517. ⟨hal-00547967⟩

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