The Platelet P2 Receptors in Thrombosis

ABSTRACT

Adenosine diphosphate (ADP) and adenosine triphosphate (ATP) play a crucial role in hemostasis and thrombosis, and their receptors are potential targets for antithrombotic drugs. The ATP-gated channel P2X₁ and the two G protein-coupled P2Y₁ and P2Y₁₂ ADP receptors selectively contribute to platelet aggregation. Because of its central role in the formation and stabilization of a thrombus, the P2Y₁₂ receptor is a well-established target of antithrombotic drugs such as clopidogrel, which has proven efficacy in many clinical trials and experimental models of thrombosis. Competitive P2Y₁₂ antagonists have also been shown to be effective in experimental thrombosis as well as in several clinical trials. Studies in P2Y₁ and P2X₁ knockout mice and experimental thrombosis models using selective P2Y₁ and P2X₁ antagonists have shown that, depending on the conditions, these receptors could also be potential targets for new antithrombotic drugs. Because both P2X₁ and P2Y₁ receptor inhibition result in milder prolongation of the bleeding time as compared with P2Y₁₂ inhibition, the idea is put forward that combinations of P2 receptor antagonists could improve efficacy with diminished hemorrhagic risk. However, further studies with stronger and more selective P2 receptor antagonists are required to validate such a point of view.

KEYWORDS

ADP - ATP - P2Y - P2X - antiplatelet drug - hemostasis

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