Platelet ADP-induced aggregation pathway

The platelet ADP-induced aggregation pathway is a physiological process essential for hemostasis and a key driver of arterial thrombosis (NIH, 1.3.1). It is triggered by the binding of adenosine diphosphate (ADP) to specific purinergic receptors on the platelet surface, primarily P2Y1 and P2Y12 (AHA, 1.2.1). P2Y1 is a Gq-coupled receptor that mediates calcium mobilization and platelet shape change, while P2Y12 is a Gi-coupled receptor that inhibits adenylyl cyclase, leading to decreased intracellular cAMP levels (NIH, 1.2.2). This signaling synergy results in the activation of the integrin alpha-IIb/beta-3 (GPIIb/IIIa) complex, which facilitates platelet-to-platelet bridging via fibrinogen (NIH, 1.3.2). Because of its central role in thrombus stabilization, the P2Y12 receptor within this pathway is the primary target for several blockbuster antiplatelet medications, including clopidogrel, prasugrel, and ticagrelor (ASH, 1.2.3). These drugs are standard of care for preventing secondary ischemic events in patients with acute coronary syndromes or those undergoing percutaneous coronary intervention (AHA, 1.2.4).

Other names

ADP-induced platelet aggregationPlatelet P2Y receptor signalingADP-P2Y12/P2Y1 pathwayPlatelet purinergic signaling

The pathway is targeted primarily through the antagonism of the P2Y12 receptor, which prevents the Gi-protein-mediated inhibition of adenylyl cyclase (NIH, 1.3.1). This maintains high levels of intracellular cyclic AMP (cAMP), which in turn inhibits the activation of the integrin alpha-IIb/beta-3 (GPIIb/IIIa) receptor (NIH, 1.2.5). Additionally, experimental antagonists target the P2Y1 receptor to block Gq-mediated calcium mobilization and platelet shape change (AHA, 1.2.1).