4.0 Article Proceedings Paper

The platelet P2 receptors in arterial thrombosis

期刊

BLOOD CELLS MOLECULES AND DISEASES
卷 36, 期 2, 页码 223-227

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bcmd.2005.12.024

关键词

haemostasis; thrombosis; ADP; ATP; P2Y(1); P2Y(12); P2X(1); antiplatelet drugs; clopidogrel

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ADP and ATP play a crucial role in hemostasis and thrombosis and their receptors are potential targets for antithrombotic drugs. The ATP-gated channel P2X(1) and the two G protein-coupled P2Y(1) and P2Y(12) ADP receptors selectively contribute to platelet aggregation. 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 clopidogrel which has proved efficacious 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) knock-out 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. Since both P2X(1) and P2Y(1) receptor inhibition result in milder prolongation of the bleeding time as compared to P2Y(12) inhibition, the idea is put forward that combination of P2 receptor antagonists could improve efficacy with diminished hemorrhagic risk. However, further studies are required to validate such a point of view. (c) 2006 Elsevier Inc. All rights reserved.

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