Cholera toxin-induced changes in force of contraction and cyclic AMP levels in canine ventricular myocardium: inhibition by carbachol.

Cholera toxin (1-10 micrograms/ml) had a biphasic inotropic action on the isolated canine ventricular muscle: it produced a transient negative and a long lasting positive inotropic effect. The negative effect reached a maximum 43 +/- 2 min (n = 12) after administration of the toxin, while it took 3-5 hrs for the positive effect to reach a steady level. The positive inotropic effect of cholera toxin was accompanied by a prominent abbreviation of the time to peak tension and the relaxation time of individual contractions. The level of adenosine 3',5'-cyclic monophosphate (cyclic AMP) of the tissue was elevated by cholera toxin in a time- and concentration-dependent manner. Carbachol (1 mumol/l) administered 3 or 5 hrs after the administration of cholera toxin (10 micrograms/ml) reversed the increase in force of contraction and the elevation of cyclic AMP levels induced by cholera toxin. These results indicate that cholera toxin exerts a cyclic AMP-dependent positive inotropic effect and a negative inotropic effect which is not related to cyclic AMP levels in canine ventricular myocardium.