Purinergic P2Y receptor (P2YR)

Purinergic P2Y receptors are a family of G protein-coupled receptors (GPCRs) that are activated by extracellular nucleotides such as ATP, ADP, UTP, and UDP (IUPHAR/BPS Guide to Pharmacology). These receptors are essential for mediating diverse biological functions, including platelet aggregation, vascular tone regulation, and immune cell modulation (Nature Reviews Drug Discovery). The family consists of eight distinct human subtypes (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14), which are divided into two subgroups based on their G protein coupling: the Gq-coupled P2Y1-like subgroup and the Gi-coupled P2Y12-like subgroup (PubMed). Clinically, the P2Y12 receptor is a major therapeutic target for antiplatelet drugs like clopidogrel and ticagrelor, which are used to prevent myocardial infarction and stroke (StatPearls). Additionally, P2Y2 receptor agonists such as diquafosol are employed to treat dry eye syndrome by promoting ocular fluid and mucin secretion (NIH). Because of their wide expression across the cardiovascular, nervous, and immune systems, P2Y receptors are also being investigated as targets for treating chronic pain, neuroinflammation, and metabolic disorders (UniProt).

Other names

P2Y purinoceptorMetabotropic purinergic receptorP2Y familyNucleotide receptor

Drugs targeting P2Y receptors primarily function as either selective antagonists to inhibit ADP-induced platelet aggregation (specifically targeting the P2Y12 subtype) or as agonists to stimulate fluid and mucin secretion in mucosal tissues (specifically targeting the P2Y2 subtype).