ADP receptors of platelets and their inhibition

ADP plays a crucial role in haemostasis and thrombosis and its receptors ar e potential targets for antithrombotic drugs. Two G-protein coupled P2 rece ptors contribute to platelet aggregation: the P2Y(1) receptor initiates agg regation through mobilisation of calcium stores, while the more recently id entified P2Y(12) receptor coupled to adenylyl cyclase inhibition is essenti al for a full aggregation response to ADP and the stabilisation of aggregat es. The latter is defective in certain patients with a selective congenital deficiency of aggregation to ADP. It is also the target of the antithrombo tic drug clopidogrel and of ATP analogues and other compounds currently und er evaluation. In addition, the P2X(1) ionotropic receptor is present in pl atelets but its role is not yet completely known. Studies in P2Y(1) knock-o ut mice and experimental thrombosis models using selective P2Y(1) antagonis ts have shown that the P2Y(1) receptor, like the P2Y(12) receptor, is a pot ential target for new antithrombotic drugs.