On the action of triamterene on isolated cell membranes

Abstract

Recently there have been recurring reports on extrarenal and expecially on antiarrhythmic effects of triamterene, the latter ones being observed particularly in cases of digitalis intoxication. Considering the digitalis-antagonistic effects, which are also observed in the course of experimental investigations, it was assumed that triamterene, a potassium-saving diuretic, displaces cardiac glycosides from their binding sites in cardiac membranes. The binding of [3H]-g-strophanthin ([3H]-ouabain) and the activity of the (Na+ + K+)-ATPase in the presence of different concentrations of triamterene have been studied with isolated cardiac cell membranes (human; bovine) and human erythrocyte membranes. Inhibition of the binding of the cardiac glycoside and the enzyme activity was only observed for very high concentrations of the active component. These observations are indicative of non-specific effects. Triamterene applied in the presence of different concentrations of strophanthin (10(-9)--5 X 10(-7) M) did not display protective effects on the (Na+ + K+)-ATPase activity. In experiments aimed at chromatographic separations, it could be shown that [3H]-triamterene binds to membrane proteins different from those binding [3H]-g-strophanthin, the latter having been shown to be present in the (Na+ + K+)-ATPase containing fraction. From the results of these experiments it may be concluded that there is no interaction between triamterene and strophanthin on the membrane bound receptor for the cardiac glycoside. [3H]-Triamterene shows concentration dependent binding to cell membranes. This binding is affected to different degrees by Mg++, K+, Na+ and Ca++. The binding sites show low affinity but high binding capacity for triamterene. The significance of this fact remains to be established.