Chen X S, Long K, Yue T L, Jiang Y Y, Wan W Q
Department of Pharmacology, College of Pharmacy, Second Military Medical University, Shanghai.
Yao Xue Xue Bao. 1990;25(9):658-63.
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 78.6 mumol/L. Only at higher concentration (500 mumol/L) of CI-914, was the production of 12-HETE (measured by HPLC), 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 A23187-stimulated pleural neutrophils, CI-914 caused a dose-related decrease of TXA2 production (measured by RIA), with IC50 values of 28.6 and 51.3 mumol/L, respectively. Meanwhile, significant increases of PGE2 synthesis in the platelets and 6-keto-PGF1 alpha 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.
研究了新型强心剂CI - 914对大鼠中性粒细胞和血小板体外花生四烯酸（AA）代谢的影响。使用洗涤过的大鼠血小板，发现通过环氧化酶和血栓素A2（TXA2）合成酶代谢AA产生的产物HHT（通过高效液相色谱法测定）的形成受到该药物的剂量依赖性抑制，IC50值为78.6 μmol/L。仅在较高浓度（500 μmol/L）的CI - 914作用下，血小板中脂氧合酶产物12 - 羟基二十碳四烯酸（12 - HETE，通过高效液相色谱法测定）的产生才受到抑制。这些结果表明，CI - 914主要通过抑制环氧化酶和TXA2合成酶而不是脂氧合酶来抑制AA代谢。在大鼠血小板和A23187刺激的胸膜中性粒细胞中，CI - 914导致TXA2产生（通过放射免疫分析法测定）呈剂量相关下降，IC50值分别为28.6和51.3 μmol/L。同时，当CI - 914与这些细胞预孵育时，观察到血小板中前列腺素E2（PGE2）合成以及胸膜中性粒细胞中6 - 酮 - 前列腺素F1α（6 - keto - PGF1α）合成显著增加。提示CI - 914可能选择性抑制大鼠血小板和胸膜中性粒细胞中TXA2合成酶的活性。
