P2Y1

P2Y1 is a purinergic G protein-coupled receptor (GPCR) that binds extracellular nucleotides, with adenosine diphosphate (ADP) as its principal endogenous agonist. It belongs to the P2Y family of receptors and is activated through coupling with the Gq/11 family of G proteins.

Upon activation, P2Y1 stimulates phospholipase C via Gq/11, leading to the production of inositol trisphosphate (IP3) and diacylglycerol (DAG). This signaling cascade increases intracellular calcium levels, triggering various calcium-dependent responses. In platelets, P2Y1 contributes to shape change and, together with the P2Y12 receptor, promotes ADP-induced platelet aggregation, a key step in hemostasis and thrombus formation. P2Y1 also participates in purinergic signaling in other tissues, including vascular smooth muscle and certain brain cells, where it can influence vascular tone and astrocyte-mediated communication.

The human P2Y1 receptor is encoded by the P2RY1 gene and is a seven-transmembrane GPCR expressed in multiple tissues. Its activity is modulated by extracellular ADP, with ATP acting as a less potent agonist for this receptor in some contexts. Pharmacological tools, including selective antagonists and agonists, are used in research to dissect P2Y1 function and its interaction with other purinergic receptors, notably P2Y12, in platelet responses. Mouse models lacking P2Y1 have helped clarify its role in thrombus formation and vascular signaling, underscoring its importance in purinergic physiology.