P2 receptors, platelet function and pharmacological implications

• Published in: Thrombosis and haemostasis Vol. 99; no. 3; p. 466
• Main Author: Gachet, Christian
• Format: Journal Article
• Language: English
• Published: Germany 01.03.2008
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Triphosphate - metabolism; Animals; Atherosclerosis - blood; Atherosclerosis - drug therapy; Atherosclerosis - metabolism; Blood Coagulation - drug effects; Blood Platelets - drug effects; Blood Platelets - metabolism; Fibrinolytic Agents - pharmacology; Fibrinolytic Agents - therapeutic use; Humans; Inflammation - blood; Inflammation - drug therapy; Inflammation - metabolism; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - metabolism; Mice; Mice, Knockout; Neovascularization, Physiologic - drug effects; Platelet Activation - drug effects; Polymorphism, Genetic; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2 - genetics; Receptors, Purinergic P2 - metabolism; Receptors, Purinergic P2X; Receptors, Purinergic P2Y1; Receptors, Purinergic P2Y12; Signal Transduction - drug effects; Thrombosis - blood; Thrombosis - drug therapy; Thrombosis - genetics; Thrombosis - metabolism
• ISSN: 0340-6245
• DOI: 10.1160/TH07-11-0673

ADP and ATP play a crucial role in platelet activation and their receptors are potential targets for antithrombotic drugs. The ATP-gated cation channel P2X(1) and the two G protein-coupled ADP receptors, P2Y(1) and P2Y(12), selectively contribute to platelet aggregation and formation of a thrombus. Owing to its central role in the growth and stabilization of a thrombus, the P2Y(12) receptor is an established target of antithrombotic drugs like the thienopyridines clopidogrel or prasugrel, or competitive antagonists such as cangrelor or AZD6140. The optimal inhibition of this receptor to reach clinical efficacy while preserving patients from unacceptable bleeding is a matter of debate. On the other hand, studies in P2Y(1) and P2X(1) knockout mice and using selective P2Y(1) and P2X(1) antagonists have shown that these receptors are also attractive targets for new antithrombotic compounds. Finally, the regulation by the P2 receptors of the platelet involvement in inflammatory processes is also briefly discussed.