Staurosporine inhibits the anaphylactic reaction of the isolated guinea-pig heart.
Isolated hearts from ovalbumin sensitized guinea-pigs were perfused according to Langendorff. Ovalbumin injection decreased coronary flow. Left ventricular pressure amplitude and heart rate increased initially and decreased thereafter. Concomitantly, the liberation of histamine, prostaglandin F2 alpha, as well as the sum of leukotrienes C4/D4/E4/F4, measured in the perfusate by radioimmunoassay, was augmented. Staurosporine (1 microM), an inhibitor of protein kinases, did not influence the liberation of mediators in response to antigen challenge, but inhibited all mechanical responses. Infusion of phorbol myristate acetate, an activator of protein kinase C, into non-sensitized hearts decreased coronary flow and left ventricular pressure amplitude, but did not liberate mediators. Staurosporine (1 microM) abolished these mechanical responses. The results indicate that staurosporine suppresses cardiac anaphylaxis by blockage of mediator effects rather than by inhibition of liberation or formation of mediators.
Schäfer
S
S
Department of Pharmacology, Boehringer Ingelheim KG, Ingelheim, Germany.
Walland
A
A
D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000707:Anaphylaxis / Q000188:drug therapy*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D003326:Coronary Circulation / Q000187:drug effects; D015237:Dinoprost / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D010047:Ovalbumin; D011863:Radioimmunoassay; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D017725:Ventricular Pressure / Q000187:drug effects
D000470:Alkaloids; D001095:Arachidonic Acids; D015289:Leukotrienes; D010047:Ovalbumin; D015237:Dinoprost; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate