P2 receptors, platelet function and pharmacological implications.
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.
Gachet
Christian
C
Institut National de la Santé et de la Recherche Médicale, U311, Strasbourg, France. christian.gachet@efs-alsace.fr
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D011110:Polymorphism, Genetic; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D015398:Signal Transduction / Q000187:drug effects; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D005343:Fibrinolytic Agents; D008565:Membrane Proteins; C546382:P2RY1 protein, human; C548576:P2RY12 protein, human; C546383:P2ry1 protein, mouse; C548577:P2ry12 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate