The platelet P2 receptors as molecular targets for old and new antiplatelet drugs

Platelet activation by ADP and ATP plays a crucial role in haemostasis and thrombosis, and their so-called P2 receptors are potential targets for antithrombotic drugs. The ATP-gated channel P2X(1) and the 2 G protein-coupled P2Y(1) and P2Y(12) ADP receptors selectively contribute to platelet aggregation. The P2Y(1) receptor is responsible for ADP-induced shape change and weak and transient aggregation, while the P2Y(12) receptor is responsible for the completion and amplification of the response to ADP and to all platelet agonists, including thromboxane A(2) (TXA(2)), thrombin, and collagen. The P2X(1) receptor is involved in platelet shape change and in activation by collagen under shear conditions. Due to its central role in the formation and stabilization of a thrombus, the P2Y(12) receptor is a well-established target of antithrombotic drugs like ticlopidine or clopidogrel, which have proved efficacy in many clinical trials and experimental models of thrombosis. Competitive P2Y(12) antagonists have also been shown to be effective in experimental thrombosis as well as in several clinical trials. Studies in P2Y(1) and P2X(1) knockout mice and experimental thrombosis models using selective P2Y(1) and P2X(1) antagonists have shown that, depending on the conditions, these receptors could also be potential targets for new antithrombotic drugs. (c) 2005 Elsevier Inc. All rights reserved.