P2Y2 purinoceptor (IPR000356)
Short name: P2Y2_rcpt
Overlapping homologous superfamilies
- G protein-coupled receptor, rhodopsin-like (IPR000276)
- P2Y2 purinoceptor (IPR000356)
There are three distinct families of extracellular receptors for purine and pyrimidine nucleotides [PMID: 9364468], known as P1, P2X and P2Y purinoceptors [PMID: 19921464]. These receptors induce a wide variety of biological effects and are involved in many different cellular functions [PMID: 10629443, PMID: 20471713, PMID: 11099464]. P2X receptors are ligand-gated ion channels, whereas P1 and P2Y receptors are rhodopsin-like G protein-coupled receptors [PMID: 7724657, PMID: 8872457]. The families also differ by their method of activation: P1 receptors are preferentially activated by adenosine [PMID: 11734617], P2X via ATP [PMID: 12270951], whereas the P2Y receptors, in addition to being activated by ATP, are activated by different adenine and/or uridine nucleoside di- and triphosphates (ADP, UDP, UTP, UDP and UDP-glucose) [PMID: 16257449].
The P2Y purinoceptors currently consist of eleven subtypes: P2Y1, P2Y2, P2Y3 P2Y4, P2Y6, P2Y8, P2Y10, P2Y11, P2Y12, P2Y13 and P2Y14 [PMID: 16968944, PMID: 11004484, PMID: 9755289]. P2Y3 has, as yet, only been found in birds [PMID: 8508924], whilst the rest have been cloned in humans. The gaps in P2Y receptor numbering are due to the reclassification of some receptors that were initially associated with to the P2Y family. These include P2Y5 (now known as lysophosphatidic acid receptor 6), P2Y7 (now leukotriene B4 receptor) and P2Y9 (lysophosphatidic acid receptor 4) [PMID: 19386608, PMID: 8921391, PMID: 8702478, PMID: 12724320].
P2Y purinoceptor subtypes have different pharmacological selectivities, which overlap in some cases, for various adenosine and uridine nucleotides. They are widely expressed and are involved in platelet aggregation, vasodilation and neuromodulation, and a range of other processes, such as ion flux, differentiation, and synaptic communication [PMID: 11794691, PMID: 16914897, PMID: 16934527, PMID: 16257449]. They exert their varied biological functions based on different G-protein coupling [PMID: 11111826]. Each receptor subtype can couple to multiple G proteins, either Gi, Gq/11 or Gs, triggering the activation of diverse intracellular signalling cascades (stimulation of phospholipase C through Gq/11, stimulation of adenylyl cyclase via Gs, or ihibition of adenylyl cyclase via Gi [PMID: 18404483, PMID: 9755289]).
This entry represents the P2Y2 receptor (previously known as nucleotide receptor P2U). It is expressed in in various epithelial cells [PMID: 16139976, PMID: 19011163, PMID: 19223794, PMID: 15558320], aortic smooth muscle [PMID: 7779087, PMID: 11690642] and the brain [PMID: 16874807, PMID: 11690642]. It is activated by both adenine and uracil nucleotides and triphosphates but not diphosphates [PMID: 7685114, PMID: 8700127]. P2Y2 receptors couple mainly to Gq/11 [PMID: 17609252]. In bronchial and intestinal epithelia, receptor activation leads to stimulation of chloride secretion and inhibition of Na+ transport [PMID: 17291397, PMID: 15704203, PMID: 16056234]. As a result, P2Y2 is a potential drug target for treating cystic fibrosis [PMID: 16495779]. P2Y2 receptor agonists have been shown to enhance ciliary beat frequency and modulate mucin release in animals [PMID: 18635403, PMID: 12458155, PMID: 15704203]. In vascular endothelial cells and vascular smooth muscle cells, the activation of P2Y2 receptors by ATP/UTP induces the tyrosine phosphorylation and activation of the ERK1 and ERK2 MAP kinases [PMID: 8882634, PMID: 9746468]. The receptor mediates vasodilation to increase coronary blood [PMID: 8779921].
GO:0045028 G-protein coupled purinergic nucleotide receptor activity
GO:0016021 integral component of membrane