Potentiation by higenamine of the aconitine-induced positive chronotropic effect in isolated right atria of mice: the effects of cholera toxin, forskolin and pertussis toxin.
Aconitine and higenamine are the major cardioactive compounds obtained from processed aconite. The chronotropic interaction between these two compounds was investigated in isolated right atria of mice. Both aconitine and higenamine potentiated the action of the other. Practolol (1 nM), a selective beta 1-adrenergic antagonist, but not butoxamine (1 microM), a beta 2-adrenergic antagonist, blocked the potentiation by higenamine (5 nM) of the aconitine-induced positive chronotropic effect and, at high concentrations (30 and 300 nM) also shifted the aconitine concentration-response curves to the right. The potentiating interaction between aconitine and higenamine was reversed by pretreating with cholera toxin (CTX) and forskolin. In CTX (100 nM, 1 h)- and forskolin (30 and 100 nM)-treated atria, higenamine significantly depressed the aconitine-induced response, which was abolished by pertussis toxin (PTX, 150 micrograms/kg, i.p., 3 d). Neither CTX (50 and 100 nM) nor forskolin (15-100 nM) significantly affected the aconitine-induced positive chronotropic effect, while PTX (150 micrograms/kg) depressed it. These results suggest that the potentiating interaction between aconitine and higenamine involves "cross-talk" between the beta 1-adrenergic signalling pathway and Gi-protein.
Kimura
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Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Islam
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MA
Kimura
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D000157:Aconitine / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D004357:Drug Synergism; D019204:GTP-Binding Proteins / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D051379:Mice; D037342:Pertussis Toxin; D011217:Practolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D013268:Stimulation, Chemical; D044005:Tetrahydroisoquinolines; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000470:Alkaloids; D011943:Receptors, Adrenergic, beta; D044005:Tetrahydroisoquinolines; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D011217:Practolol; C012348:higenamine; D000157:Aconitine