陈新生, 龙焜, 岳天立, 姜远英, 万维勤. 咪苯嗪酮对TXA2和HHT生成的选择性抑制作用J. 药学学报, 1990, 25(9): 658-663.
引用本文: 陈新生, 龙焜, 岳天立, 姜远英, 万维勤. 咪苯嗪酮对TXA2和HHT生成的选择性抑制作用J. 药学学报, 1990, 25(9): 658-663.
XS Chen, K Long, TL Yue, YY Jiang , WQ Wan, . SELECTIVE INHIBITION OF CI-914 ON THE PRODUCTION OF TXA2 AND HHTJ. Acta Pharmaceutica Sinica, 1990, 25(9): 658-663.
Citation: XS Chen, K Long, TL Yue, YY Jiang , WQ Wan, . SELECTIVE INHIBITION OF CI-914 ON THE PRODUCTION OF TXA2 AND HHTJ. Acta Pharmaceutica Sinica, 1990, 25(9): 658-663.

咪苯嗪酮对TXA2和HHT生成的选择性抑制作用

SELECTIVE INHIBITION OF CI-914 ON THE PRODUCTION OF TXA2 AND HHT

  • 摘要: 咪苯嗪酮(CI-914)能抑制大鼠血小板环氧酶和TXA2合成酶产物HHT的生成,而对脂氧酶产物12-HETE的生成仅高浓度药物才有弱的抑制作用,提示CI-914主要影响花生四烯酸(AA)环氧酶途径,而对脂氧酶途径影响较少。在大鼠血小板和中性白细胞CI-914能抑制TXA2的生成,同时CI-914还可使白细胞6-keto-PGF1a和血小板PGE2的产生量显著增加,提示CI-914在这两种细胞引起了AA的转向合成。上述结果基本证实,CI-914在大鼠中性白细胞和血小板对TXA2合成酶具有选择性抑制作用。

     

    Abstract: The effects of CI-914, a novel cardiotonic agent, on AA metabolism in rat neutrophils and platelets in vitro were investigated. Using washed rat platelets, the formation of HHT (measured by HPLC), a product of AA metabolism via cyclooxygenase and TXA2 synthetase, was found to be inhibited by the agent in a dose-dependent manner, with IC50 value of 78.6μmol/L. Only at higher concentration (500μmol/L) of CI-914, was the production of 12-HETE (measured by HP LC), a lipoxygenase product in platelets, shown to be inhibited. These indicate that CI-914. mainly inhibits the metabolism of AA via cyclooxygenase and TXA2 synthetase rather than via lipoxygenase. In rat platelets and A23187stimulated pleural neutrophils, CI-914 caused a dose-related decrease of TXA2 production (measured by RIA), with IC50 values of 28.6 and 51.3μmol/L , respectively. Meanwhile, significant increases of PGE2 synthesis in the platelets and 6-keto-PGF synthesis in the pleural neutrophils were observed when CI-914 was preincubated with these cells. It is suggested that CI-914 might selectively inhibit the activity of TXA2 synthetase in rat platelets and pleural neutrophils.

     

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