Update of P2Y receptor pharmacology : IUPHAR Review 27

Jacobson, Kenneth A. and Delicado, Esmerilda G. and Gachet, Christian and Kennedy, Charles and von Kügelgen, Ivar and Li, Beibei and Miras-Portugal, M. Teresa and Novak, Ivana and Schöneberg, Torsten and Perez-Sen, Raquel and Thor, Doreen and Wu, Beili and Yang, Zhenlin and Müller, Christa E. (2020) Update of P2Y receptor pharmacology : IUPHAR Review 27. British Journal of Pharmacology, 177 (11). 2413–2433. ISSN 1476-5381

[thumbnail of Jacobson-etal-2020-Update-of-P2Y-Receptor=pharmacology-IUPHAR]
Preview
 Text (Jacobson-etal-2020-Update-of-P2Y-Receptor=pharmacology-IUPHAR)
Jacobson_etal_2020_Update_of_P2Y_Receptor_pharmacology_IUPHAR.pdf
Accepted Author Manuscript
Download (2MB)| Preview

    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.

    ORCID iDs

    Jacobson, Kenneth A., Delicado, Esmerilda G., Gachet, Christian, Kennedy, Charles ORCID logoORCID: https://orcid.org/0000-0001-9661-5437, von Kügelgen, Ivar, Li, Beibei, Miras-Portugal, M. Teresa, Novak, Ivana, Schöneberg, Torsten, Perez-Sen, Raquel, Thor, Doreen, Wu, Beili, Yang, Zhenlin and Müller, Christa E.;
    • Item type:Article
      ID code:72461
      Dates:
      Date
      Event
      9 February 2020
      Published
      9 February 2020
      Published Online
      22 January 2020
      Accepted
      Keywords:GPCR, G protein-coupled receptor, nucleotide receptors, P2Y receptors, nucleotides, Pharmacy and materia medica, Pharmacology, Toxicology and Pharmaceutics(all)
      Subjects:Medicine > Pharmacy and materia medica
      Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
      Depositing user: Pure Administrator
      Date deposited:26 May 2020 10:23
      Last modified:23 Sep 2021 07:44
      URI:https://strathprints.strath.ac.uk/id/eprint/72461
    CORE (COnnecting REpositories)