Schäfer S, Walland A
Department of Pharmacology, Boehringer Ingelheim KG, Ingelheim, Germany.
Methods Find Exp Clin Pharmacol. 1995 Sep;17(7):469-76.
Isolated hearts from guinea pigs were perfused at 37 degrees C with Tyrode's solution according to the technique of Langendorff. Coronary flow, left ventricular pressure amplitude and heart rate were measured. Bolus injection of 30 ng leukotriene C4 caused a long-lasting decrease in coronary flow and left ventricular pressure amplitude while heart rate was not affected. A similar but shorter lasting effect was induced by 100 ng leukotriene D4. The effects of the leukotrienes were completely blocked by 1 microM staurosporine. Staurosporine at concentrations of 100 and 10 nM, in contrast to 1 microM, influenced basic cardiac function slightly or not at all, but antagonized the effects of 30 ng leukotriene C4. In isolated tracheal muscle preparations, leukotriene C4 and D4 induced concentration-dependent contractures. Staurosporine at concentrations of 25-100 nM antagonized the effects of leukotriene C4 and D4 in a noncompetitive manner with inhibitor constants of 47.6 and 75.9 nM, respectively. The results indicate that staurosporine is a potent noncompetitive antagonist of the effects of leukotriene C4 and D4 in smooth muscle.
根据Langendorff技术，将豚鼠离体心脏在37℃用台氏液灌注。测量冠状动脉血流量、左心室压力振幅和心率。静脉注射30 ng白三烯C4导致冠状动脉血流量和左心室压力振幅长期下降，而心率未受影响。100 ng白三烯D4引起类似但持续时间较短的效应。白三烯的作用被1 μM星形孢菌素完全阻断。与1 μM相比，100 nM和10 nM浓度的星形孢菌素对基础心脏功能影响轻微或无影响，但可拮抗30 ng白三烯C4的作用。在离体气管肌肉制备物中，白三烯C4和D4诱导浓度依赖性收缩。25 - 100 nM浓度的星形孢菌素以非竞争性方式拮抗白三烯C4和D4的作用，抑制常数分别为47.6和75.9 nM。结果表明，星形孢菌素是白三烯C4和D4在平滑肌中作用的有效非竞争性拮抗剂。
