Role of P2Y receptor subtypes in platelet-derived microparticle generation

Abstract

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.

Role of Platelet-Derived Microvesicles As Crosstalk Mediators in Atherothrombosis and Future Pharmacology Targets: A Link between Inflammation, Atherosclerosis, and Thrombosis

“…Other platelet stimuli are proinflammatory mediators [like lipopolysaccharide (Stahl et al, 2011), cytokines (Nomura et al, 2000), and soluble CD40 ligand (Prasad et al, 2003)], PAR agonists (Chung et al, 2004), thrombin receptor activating peptide (Tschuor et al, 2008), and prolyl gallate (Xiao et al, 2002), among others. Regarding ADP, the P2Y12 receptor contributes to pMV formation from activated platelet surfaces without any significant involvement of the P2Y1 receptor (Kahner et al, 2008). …”

Coagulation, platelet activation and thrombosis in xenotransplantation

“…In contrast, observed induction, association of procoagulant TF on human platelets by porcine endothelial cell or both seem to occur independently of these factors [31]. As microparticles are released from platelets upon activation and contribute to clot formation, the inhibition of platelet activation is essential for reducing immune-mediated injury, and several promising approaches have been described [32].…”

“…CD39 and TF are contained within plasma microparticles, which exhibit modulatory roles in the exchange of regulatory signals between leukocytes and endothelium [5 ]. Interestingly, the P2Y12 receptor contributes to the formation of platelet microparticles [32]. Work is ongoing to analyze the nature and role of microparticles in the xenotransplantation context.…”

Erosive Arthritis and Hepatic Granuloma Formation Induced by Peptidoglycan Polysaccharide in Rats Is Aggravated by Prasugrel Treatment

“…Platelet-derived microparticles have been directly involved with leukocyte activation, monocytes in particular, during inflammation [28]. Prasugrel and clopidogrel are considered selective antagonists of the P2Y 12 receptor in platelets and inhibit platelet microparticle generation [29]. Yet, studies treating animals with thienopyridine compounds in the erosive arthritis model suggest an effect of the active or inactive metabolites of the drug in cells other than platelets, resulting in exacerbation of the inflammatory response.…”