Sanguinarine: a positive inotropic alkaloid which inhibits cardiac Na+,K+-ATPase

In isolated, isometrically contracting left guinea pig atria, sanguinarine, a benzophenanthridine alkaloid from the papaveracea Sanguinaria canadensis, produced a concentration-dependent positive inotropic effect. Between 2.3 x 10(-6) M and 6.5 x 10(-5) M, sanguinarine increased contractility by 108% which was comparable to the maximal inotropic effect of ouabain. Within the same concentration range, sanguinarine caused inhibition of Na+,K+-ATPase isolated from guinea pig myocardium. 100% inhibition of Na+,K+,ATPase activity occurred at 1 x 10(-4) M sanguinarine. The I50 for enzyme inhibition and the ED50 for the inotropic action of sanguinarine were the same (6-6.5 x 10(-6) M) indicating that both effects may be causally related.