Staurosporine inhibits the effects of leukotrienes C4 and D4 in isolated guinea pig heart and trachea.
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.
Schäfer
S
S
Department of Pharmacology, Boehringer Ingelheim KG, Ingelheim, Germany.
Walland
A
A
D000470:Alkaloids / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019311:Staurosporine; D014132:Trachea / Q000187:drug effects*; D016277:Ventricular Function, Left / Q000187:drug effects
D000470:Alkaloids; D004791:Enzyme Inhibitors; D017997:Leukotriene C4; D017998:Leukotriene D4; D019311:Staurosporine