P2Y purinoceptor 1 and P2Y purinoceptor 12 (P2Y1 / P2Y12)

The P2Y1 and P2Y12 receptors are G protein-coupled receptors (GPCRs) that function as the primary mediators of adenosine diphosphate (ADP)-induced platelet activation [6, 13]. P2Y1 (P2RY1) is coupled to the Gq protein and initiates platelet shape change and transient aggregation by mobilizing intracellular calcium [3, 5, 17]. In contrast, P2Y12 (P2RY12) is coupled to the Gi protein and is essential for stabilizing platelet aggregates and amplifying the overall aggregation response by inhibiting adenylyl cyclase [1, 9, 20]. These receptors are critical for normal hemostasis but also drive the formation of pathological thrombi in cardiovascular diseases such as acute coronary syndrome and stroke [8, 15]. P2Y12 is a major therapeutic target, with several widely used antiplatelet drugs, including clopidogrel, prasugrel, and ticagrelor, acting as antagonists to prevent ischemic events [7, 12, 23]. While P2Y12 inhibitors are the clinical standard, dual inhibition of both P2Y1 and P2Y12 is being explored to provide more comprehensive antiplatelet therapy [2]. The most significant safety concern associated with these drugs is an increased risk of major bleeding [11, 24].

Other names

Purinergic receptor P2Y1Purinergic receptor P2Y12ADP receptorsP2RY1P2RY12Platelet ADP receptors

Antagonism of ADP-induced platelet activation via inhibition of P2Y1 and/or P2Y12 receptors, preventing platelet aggregation and thrombus stabilization.