Update of P2Y receptor pharmacology: IUPHAR Review 27

Br J Pharmacol. 2020 Jun;177(11):2413-2433. doi: 10.1111/bph.15005. Epub 2020 Apr 6.


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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Neurons
  • Purinergic P2Y Receptor Agonists*
  • Purinergic P2Y Receptor Antagonists*
  • Receptors, G-Protein-Coupled*
  • Receptors, Purinergic P2Y1
  • Signal Transduction*


  • Purinergic P2Y Receptor Agonists
  • Purinergic P2Y Receptor Antagonists
  • Receptors, G-Protein-Coupled
  • Receptors, Purinergic P2Y1