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 tw o compounds mas investigated in isolated right atria of mice, Both aco nitine and higenamine: potentiated the action of the other, Practolol (1 nM), a selective beta(1)-adrenergic antagonist, but not butoxamine (1 mu m), a beta(2)-adrenergic antagonist, blocked the potentiation by higenamine (5 nM) of the aconitine-induced positive chronotropic effe ct and, at high concentrations (30 and 300 nM) also shifted the aconit ine concentration-response curves to the right. The potentiating inter action between aconitine and higenamine was reversed by pretreating wi th cholera toxin (CTX) and forskolin, In CTX (100 nM, 1 h)- and forsko lin (30 and 100 nM)-treated atria, higenamine significantly depressed the aconitine-induced response, which was abolished by pertussis toxin (PTX, 150 mu g/kg, i.p., 3d). Neither CTX (50 and 100 nM) nor forskol in (15-100 nM) significantly affected the aconitine-induced positive c hronotropic effect, while TX (150 mu g/kg) depressed it. These results suggest that the potentiating interaction between aconitine and higen amine involves ''cross-talk'' between the beta(1)-adrenergic signallin g pathway and G(i)-protein.