Pharmacology and structure of P2Y receptors

P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides. There are eight mammalian P2Y receptor subtypes (P2Y(1), P2Y(2), P2Y(4), P2Y(6), P2Y(11), P2Y(12), P2Y(13), and P2Y(14)). P2Y receptors are widely expressed and play important roles in physiology and pathophysiology. One important example is the ADP-induced platelet aggregation mediated by P2Y(1) and P2Y(12) receptors. Active metabolites of the thienopyridine compounds ticlopidine, clopidogrel and prasugrel as well as the nucleoside analogue ticagrelor block P2Y(12) receptors and thereby platelet aggregation. These drugs are used for the prevention and therapy of cardiovascular events. Moreover, P2Y receptors play important roles in the nervous system. Adenine nucleotides modulate neuronal activity and neuronal fibre outgrowth by activation of P2Y(1) receptors and control migration of microglia by P2Y(12) receptors. UDP stimulates microglial phagocytosis through activation of P2Y(6) receptors. There is evidence for a role for P2Y(2) receptors in Alzheimer's disease pathology. The P2Y receptor subtypes are highly diverse in both their amino acid sequences and their pharmacological profiles. Selective receptor ligands have been developed for the pharmacological characterization of the receptor subtypes. The recently published three-dimensional crystal structures of the human P2Y(1) and P2Y(12) receptors will facilitate the development of therapeutic agents that selectively target P2Y receptors. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. (C) 2015 Elsevier Ltd. All rights reserved.