デクスメデトミジンはα2アドレナリン受容体を介してヒト血小板由来マイクロパーティクル産生を増加させる

Abstract

Background: Dexmedetomidine (DEX) is a potent and highly selective agonist of the α2-adrenoceptor. Recent studies suggested that platelet-derived microparticles (PMPs) have procoagulant activity that was released from activated platelet membranes and might be involved in thrombogenesis. In the present study, we examined the effects of DEX on PMP generation in human platelets by flow cytometry. Methods: Platelet rich plasma was prepared from healthy male volunteers who had not taken any medication for at least for two weeks before blood collection. The platelet rich plasma was placed at room temperature for 30 min with or without DEX (1, 10, 100 ng/mL) without any stimulant ligands in the presence or absence of yohimbine (10μM), an α2-antagonist. PMPs were identified using flow cytometry by forward and side scatter intensity and by CD61 and Annexin V expression, and the percentage of PMP counts in platelets was calculated. All data were compared with one-way analysis of variance (ANOVA), followed by Dunnett’s post hoc test. A P value less than 0.05 indicates statistical significance. Result: DEX (10, 100 ng/mL) increased PMP generation in a dose-dependent manner, and this effect was abolished by yohimbine. Discussion: Previously we reported that DEX has both enhancing and suppressing effects on human platelet functions via the α2-adrenoceptor and imidazoline 1-receptor, respectively. Although DEX enhanced platelet aggregation and P-selectin expression, its effects on PMP generation have not been examined. In this study, we found that DEX promoted PMP generation, and this response was abolished by yohimbine, indicating that DEX increases PMP generation via the α2-adrenoceptor. Although our study was performed in vitro, and the concentration of DEX that affected PMP generation was apparently higher than the usual therapeutic concentration range (<1 ng/mL), the elevated PMP counts induced by DEX may be responsible for the thrombotic tendency. Conclusion: DEX increases PMP generation via the α2-adrenoceptor in human platelets.