MN-9202对兔血小板聚集、5-HT释放、TXB_2合成及Ca~(2 )转运的影响(英文)

目的:研究新二氢吡啶类钙拮抗剂MN-9202对兔血小板激活的影响,并探讨其作用机制。方法:以Fu-ra-2 AM为荧光探针,采用时间扫描方式记录血小板内Ca~(2 )的变化;分别用HPLC/ECD和放射免疫测定法检测5-HT及TXB_2。结果:MN-9202剂量依赖地抑制ADP或凝血酶诱导的血小板聚集,抑制TXA_2的释放并且能有效阻滞激活血小板胞内Ca~(2 )水平的增加。MN-9202 1μmol·L~(-1)能抑制胶原15mg·L~(-1)诱导的5-HT释放反应,但对胶原45mg·L~(-1)诱导的反应无抑制作用。结论:MN-9202阻滞血小板Ca~(2 )内流并抑制血小板花生四烯酸代谢及激活反应。

Effects of MN-9202 on platelet aggregation, 5-HT release, TXB2 synthesis, and calcium mobilization in rabbit platelets in vitro

AIM: To study the effects of MN-9202, a new effective Ca2+ channel blocker, on platelet aggregation, 5-HT and TXB2 release, and calcium transport induced by platelet activators. METHODS: The mobilization of cytosolic-free calcium induced by thrombin in washed platelets was observed by Ca(2+)-sensitive fluorescent indicator, Fura-2 AM and time scan measurement. Aggregation induced by ADP and thrombin in rabbits citrate platelet-rich plasma (PRP) was measured by aggregometer. 5-HT and TXB2 were assayed by HPLC/ECD and RIA, respectively. RESULTS: MN-9202 inhibited platelet aggregation induced by ADP and thrombin in a concentration-dependent manner. MN-9202 1 mumol.L-1 inhibited release of 5-HT in PRP induced by collagen at 15 mg.L-1 (113 +/- 15 vs 178 +/- 18, P < 0.05), however, MN-9202 did not have effect on 5-HT secreted by high dose of collagen. MN-9202 0.1 and 1 mumol.L-1 blocked extracellular calcium influx and sarcoplasmic calcium release, and the suppression on extracellular calcium influx was more obvious. Furthermore, treatment with MN-9202 0.01, 0.1, and 1 mumol.L-1 markedly decreased ADP-induced TXB2 (pg/10(8) platelet) release from PRP (906 +/- 200, 881 +/- 131, and 793 +/- 169 vs 1264 +/- 202, P < 0.01). CONCLUSION: MN-9202 acts as an effective Ca2+ antagonist and blocks platelet activation by inhibiting platelet Ca2+ influx and arachidonic acid metabolism.