Effects of MN-9202 on platelet aggregation, 5-HT release, TXB_2 synthesis, and calcium mobilization in rabbit platelets in vitro  

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)

作　　者：王莉莉[1] 梅其炳[1] 赵德化[1] 郭志安[2] 

机构地区：[1]第四军医大学药理学教研室,西安中国710032 [2]西北大学化学系,西安中国710069

出　　处：《Acta Pharmacologica Sinica》2000年第7期49-52,共4页中国药理学报（英文版）

基　　金：Project supported by Creating Doctor Foundation of Medicine Teehnology, National Science and Teehnology Committee of China (№ 94-B-04).

摘　　要：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 Ca2+-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 μmol·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 μmol·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 μmol·L-1 markedly decreased ADP-induced TXB2(pg/l08 platelet) release from PRP (906±200, 881±131, and 793±169 vs 1264±202, P<0.0l). CONCLUSION; MN-9202 acts as an effective Ca2+ an-tagonist and blocks platelet activation by inhibiting platelet Ca2+ influx and arachidonic acid metabolism.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。

关 键 词：calcium channel blockers MN-9202 platelet aggregation calcium SEROTONIN thromoxane B2 FURA-2 

分 类 号：R96[医药卫生—药理学]