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

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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 β_1-adrenergic antagonist, but not butoxamine (1 μM), a β_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 μg/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 μg/kg) depresesd it. These results suggest that the potentiating interaction between aconitine and higenamine involves "cross-talk" between the β_1-adrenergic signalling pathway and G_i-protein.
公益社団法人日本薬学会の論文
1996-08-15