Identification, characterization, and inhibition of the platelet ADP receptors

Adenosine diphosphate (ADP) plays a crucial role in hemostasis and thrombosis, and its receptors are potential targets for antithrombotic drugs. Two G-protein-coupled P2 receptors contribute to platelet aggregation: the P2Y(1) receptor initiates aggregation through mobilization of calcium stores, whereas the P2Y(12) receptor coupled to adenylyl cyclase inhibition is essential for a full aggregation response to ADP and the stabilization of aggregates. The latter is defective in certain patients with a selective congenital deficiency of aggregation to ADP. It is also the target of the antithrombotic drug clopidogrel and of adenosine triphosphate analogues and other compounds currently under evaluation. In addition, the P2X(1) ionotropic receptor is present in platelets, but its role is not yet completely known. Studies in P2Y(1)-knockout mice and experimental thrombosis models using selective P2Y(1) antagonists have shown that the P2Y(1) receptor, like the P2Y(12) receptor, is a potential target for new antithrombotic drugs. Int J Hematol. 2001;74:375-381. (C) 2001 The Japanese Society of Hematology.