Fiche publication
Date publication
février 2020
Journal
British journal of pharmacology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GACHET Christian
Tous les auteurs :
Jacobson KA, Delicado EG, Gachet C, Kennedy C, von Kügelgen I, Li B, Miras-Portugal MT, Novak I, Schöneberg T, Perez-Sen R, Thor D, Wu B, Yang Z, Müller CE
Lien Pubmed
Résumé
Eight G protein-coupled P2Y receptor (P2YR) subtypes respond to extracellular adenine and uracil mono- and dinucleotides. P2YRs belong to the δ group of rhodopsin-like GPCRs and contain two structurally distinct subfamilies: P2Y , , , , and (principally G protein-coupled P2Y -like) and P2Y (principally G protein-coupled P2Y -like) receptors. Brain P2YRs occur in neurons, glial cells and vasculature. Endothelial P2Y , P2Y , P2Y and P2Y Rs induce vasodilation, while smooth muscle P2Y , P2Y and P2Y R activation leads to vasoconstriction. Pancreatic P2Y and P2Y Rs stimulate while P2Y R inhibits insulin secretion. Antagonists of P2Y R, and potentially P2Y R, are antithrombotic agents, and a P2Y /P2Y R agonist treats dry eye syndrome in Asia. P2YR agonists are generally pro-inflammatory, and antagonists may eventually treat inflammatory conditions. This article reviews recent developments in P2YR pharmacology (using synthetic agonists and antagonists), structure and biophysical properties (using X-ray crystallography, mutagenesis and modeling), physiological and pathophysiological roles, and present and potentially future therapeutic targeting.
Mots clés
G protein-coupled receptor, GPCR, P2Y receptors, nucleotide receptor, nucleotides
Référence
Br. J. Pharmacol.. 2020 Feb 9;:
