Update of P2Y receptor pharmacology: IUPHAR Review 27.

British journal of pharmacology 2020 Jun

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Eight G protein-coupled P2Y receptor subtypes respond to extracellular adenine and uracil mononucleotides and dinucleotides. P2Y receptors belong to the δ group of rhodopsin-like GPCRs and contain two structurally distinct subfamilies: P2Y1 , P2Y2 , P2Y4 , P2Y6 , and P2Y11 (principally Gq protein-coupled P2Y1 -like) and P2Y12-14 (principally Gi protein-coupled P2Y12 -like) receptors. Brain P2Y receptors occur in neurons, glial cells, and vasculature. Endothelial P2Y1 , P2Y2 , P2Y4 , and P2Y6 receptors induce vasodilation, while smooth muscle P2Y2 , P2Y4 , and P2Y6 receptor activation leads to vasoconstriction. Pancreatic P2Y1 and P2Y6 receptors stimulate while P2Y13 receptors inhibits insulin secretion. Antagonists of P2Y12 receptors, and potentially P2Y1 receptors, are anti-thrombotic agents, and a P2Y2 /P2Y4 receptor agonist treats dry eye syndrome in Asia. P2Y receptor agonists are generally pro-inflammatory, and antagonists may eventually treat inflammatory conditions. This article reviews recent developments in P2Y receptor pharmacology (using synthetic agonists and antagonists), structure and biophysical properties (using X-ray crystallography, mutagenesis and modelling), physiological and pathophysiological roles, and present and potentially future therapeutic targeting. © 2020 The British Pharmacological Society.

Citation

Kenneth A Jacobson, Esmerilda G Delicado, Christian Gachet, Charles Kennedy, Ivar von Kügelgen, Beibei Li, M Teresa Miras-Portugal, Ivana Novak, Torsten Schöneberg, Raquel Perez-Sen, Doreen Thor, Beili Wu, Zhenlin Yang, Christa E Müller. Update of P2Y receptor pharmacology: IUPHAR Review 27. British journal of pharmacology. 2020 Jun;177(11):2413-2433