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  • Title: Effects of MN-9202 on platelet aggregation, 5-HT release, TXB2 synthesis, and calcium mobilization in rabbit platelets in vitro.
    Author: Wang LL, Mei QB, Zhao DH, Guo ZA.
    Journal: Acta Pharmacol Sin; 2000 Jul; 21(7):623-6. PubMed ID: 11360670.
    Abstract:
    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.
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