Purinergic receptor P2Y12 (P2Y12) (P2Y12)

Platelet ADP receptors, primarily the Purinergic receptor P2Y12 (P2Y12) and P2Y1 subtypes, are critical mediators of platelet activation and thrombus formation [4, 11, 14]. P2Y12 is a G protein-coupled receptor (GPCR) that plays a central role in amplifying and stabilizing platelet aggregation initiated by various agonists [5, 10, 13]. It is the primary therapeutic target for a major class of antiplatelet drugs, including clopidogrel, prasugrel, and ticagrelor, which are used to prevent cardiovascular events such as myocardial infarction and stroke [2, 8, 20]. Upon activation by adenosine diphosphate (ADP), P2Y12 triggers a Gi-mediated signaling cascade that inhibits adenylyl cyclase, leading to the activation of the glycoprotein IIb/IIIa complex required for fibrinogen binding [2, 21, 30]. Beyond hemostasis, P2Y12 is also expressed on microglia in the central nervous system, where it modulates inflammatory responses and chemotaxis [9, 23]. Clinical use of P2Y12 inhibitors is a cornerstone of dual antiplatelet therapy (DAPT) but carries a significant risk of bleeding complications [7, 22, 27].

Other names

P2Y12 receptorP2RY12Platelet ADP receptorADPG-RBDPLT8HORK3P2T(AC)P2Y(AC)P2Y(ADP)P2Y(cyc)SP1999

Antagonism of the P2Y12 receptor prevents ADP from binding, which inhibits the Gi protein-mediated signaling pathway [2, 32]. This leads to a reduction in the inhibition of adenylyl cyclase, maintaining higher intracellular cAMP levels [2, 30, 31]. Elevated cAMP levels prevent the activation of the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor complex, thereby inhibiting platelet aggregation and thrombus stabilization [2, 8, 10, 21].