Triphasic inotropic response of guinea-pig papillary muscle to murrayaquinone-A isolated from Rutaceae.
Murrayaquinone-A, a carbazole alkaloid, was found to produce a triphasic inotropic response (first positive, second negative and third positive phases) of guinea-pig papillary muscle that normally paced at a slow rate of 0.2 Hz in Krebs-Henseleit solution at 30 degrees C. Murrayaquinone-A produced a concentration-dependent (10(-6) M-10(-4) M) positive inotropic effect (pD2 value 5.27 evaluated at the first phase). The triphasic pattern of inotropism of murrayaquinone-A was unaffected by reserpine, metoprolol or cimetidine treatment. Murrayaquinone-A increased the initial upstroke and the duration of the slow action potential in partially depolarized muscle (external K+ = 30 mEq). Murrayaquinone-A did not cause any positive inotropy under anoxic conditions and in the presence of 2,4-dinitrophenol and dicumarol. These results indicated that the triphasic inotropic effect of murrayaquinone-A is not mediated through a receptor mechanism but through a novel mechanism involving mitochondrial ATP production, thereby increasing the slow inward calcium current across the cardiac cell membrane via cyclic AMP converted from mitochondrial ATP.
Takeya
K
K
Department of Pharmacology, Aichi Medical University, Japan.
Itoigawa
M
M
Furukawa
H
H
D000200:Action Potentials / Q000187:drug effects; D000470:Alkaloids; D000818:Animals; D016227:Benzoquinones; D002227:Carbazoles / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008790:Metoprolol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D010946:Plants, Medicinal / Q000032:analysis*; D012110:Reserpine / Q000494:pharmacology; D013268:Stimulation, Chemical; D014475:Uncoupling Agents / Q000494:pharmacology
D000470:Alkaloids; D016227:Benzoquinones; D002227:Carbazoles; D014475:Uncoupling Agents; C062196:murrayaquinone A; D002927:Cimetidine; D012110:Reserpine; D008790:Metoprolol