Role of P2Y receptor subtypes in platelet-derived microparticle generation.
Microparticles are shed from the platelet membrane upon platelet activation by strong agonists, and they aid in clot formation. As the P2Y1 and the P2Y12 receptors differentially contribute to different platelet functions, we studied the relative contribution of the P2Y1 and P2Y12 receptors to microparticle formation from platelets. The P2Y12 receptor antagonist AR-C 69931MX, but not the P2Y1 receptor antagonist MRS2179, caused a significant decrease in the number microparticles formed by convulxin and thrombin. In addition, there was no significant decrease in microparticle formation in P2Y1 knockout mouse blood when compared to the wild type mice. These results illustrate that the P2Y12 receptor contributes to microparticle formation from activated platelets by a strong agonist, without any significant involvement of the P2Y1 receptor. We also conclude that there is no correlation in the number of microparticles circulating in vivo between the P2Y1 receptor null mice and the wild type mice under unstimulated conditions. Finally, we conclude that the increased bleeding time in the P2Y1 null mice is due to overall platelet dysfunction and not due to the decrease of circulating microparticles.
Kahner
Bryan N
BN
Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA
Dorsam
Robert T
RT
Kunapuli
Satya P
SP
D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008863:Microspheres; D008954:Models, Biological; D015539:Platelet Activation; D010974:Platelet Aggregation; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12
D008055:Lipids; C546382:P2RY1 protein, human; C548576:P2RY12 protein, human; C546383:P2ry1 protein, mouse; C548577:P2ry12 protein, mouse; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12