Platelet P2Y12 ADP receptor (P2Y12 receptor)

The Platelet P2Y12 ADP receptor is a G protein-coupled receptor expressed on the surface of platelets that plays a central role in platelet activation and aggregation in response to adenosine diphosphate (ADP), contributing to hemostasis and thrombosis. Upon binding ADP, P2Y12 receptor activation potentiates platelet aggregation by inhibiting adenylyl cyclase via Gi proteins, thereby reducing cyclic AMP levels, which promotes activation of the integrin GPIIb/IIIa necessary for platelet crosslinking and clot formation. This receptor is a major target for widely used antithrombotic drugs such as clopidogrel, prasugrel, ticagrelor, cangrelor, and ticlopidine, which act by inhibiting the receptor to reduce the risk of thrombotic cardiovascular events. Inhibition or genetic defects of P2Y12 cause reduced platelet aggregation and may lead to mild-to-moderate bleeding diatheses. The receptor also has roles in inflammation and potentially in cancer when inhibited, and is related to clinical challenges such as bleeding and drug resistance.

Other names

P2Y12 purinergic receptorPurinergic receptor P2Y, G-protein coupled, 12P2RY12Platelet ADP receptor P2Y12P2T receptor

Antagonism/inhibition of ADP binding to the P2Y12 receptor to prevent platelet activation/aggregation - Irreversible (thienopyridines: clopidogrel, prasugrel, ticlopidine) or reversible (ticagrelor, cangrelor) inhibition of the receptor