P2Y purinoceptor 1 (P2Y1)

The P2Y purinoceptor 1 (P2Y1) is a G protein-coupled receptor primarily activated by ADP, with ATP acting as an antagonist that inhibits ADP-induced calcium mobilization. It couples mainly to Gq proteins, activating phospholipase C-beta to mobilize intracellular calcium, and also engages monomeric G proteins like Rac and Rho to regulate cytoskeletal dynamics. Expressed in platelets, megakaryocytes, adipocytes, and neurons, P2Y1 mediates platelet shape change and aggregation essential for hemostasis, bone resorption, leptin secretion, nociception, angiogenesis, and synaptic plasticity. In disease contexts, it contributes to thrombosis and atherosclerosis in cardiovascular conditions, serves as a diabetes target by modulating glucose-stimulated insulin secretion in pancreatic beta cells under circadian disruption, and plays roles in inflammation, epilepsy, and tumor immunity. Pharmacologically, compounds like ivermectin activate P2Y1 to enhance insulin secretion, while selective antagonists like MRS2179 block its effects, highlighting its druggability but also risks like impaired clotting if inhibited. Overall, P2Y1 represents a key node in purinergic signaling with broad therapeutic potential tempered by hemostatic concerns.

Other names

P2Y1 receptorP2Y1 purinergic receptor

Activation by ADP leading to Gq coupling, phospholipase C-beta activation, intracellular calcium mobilization, Rac and Rho activation; antagonism by ATP inhibiting ADP-induced calcium mobilization; inhibition of adenylyl cyclase via Gi/o coupling in related subtypes but primarily Gq for P2Y1