Update of P2Y receptor pharmacology: IUPHAR Review 27

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

Research output: Contribution to journalLiterature review

5 Citations (Scopus)

Abstract

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: P2Y 1, P2Y 2, P2Y 4, P2Y 6, and P2Y 11 (principally G q protein-coupled P2Y 1-like) and P2Y 12–14 (principally G i protein-coupled P2Y 12-like) receptors. Brain P2Y receptors occur in neurons, glial cells, and vasculature. Endothelial P2Y 1, P2Y 2, P2Y 4, and P2Y 6 receptors induce vasodilation, while smooth muscle P2Y 2, P2Y 4, and P2Y 6 receptor activation leads to vasoconstriction. Pancreatic P2Y 1 and P2Y 6 receptors stimulate while P2Y 13 receptors inhibits insulin secretion. Antagonists of P2Y 12 receptors, and potentially P2Y 1 receptors, are anti-thrombotic agents, and a P2Y 2/P2Y 4 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.

Original languageEnglish
Pages (from-to)2413–2433
Number of pages21
JournalBritish Journal of Pharmacology
Volume177
Issue number11
Early online date9 Feb 2020
DOIs
Publication statusE-pub ahead of print - 9 Feb 2020

Keywords

  • GPCR
  • G protein-coupled receptor
  • nucleotide receptors
  • P2Y receptors
  • nucleotides

Cite this

Jacobson, K. A., Delicado, E. G., Gachet, C., Kennedy, C., von Kügelgen, I., Li, B., Miras-Portugal, M. T., Novak, I., Schöneberg, T., Perez-Sen, R., Thor, D., Wu, B., Yang, Z., & Müller, C. E. (2020). Update of P2Y receptor pharmacology: IUPHAR Review 27. British Journal of Pharmacology, 177(11), 2413–2433. https://doi.org/10.1111/bph.15005