Correlation between inhibition of (Na+, K+)-membrane-ATPase and positive inotropic activity of cardenolides in isolated papillary muscles of guinea pig.
Concentrations of 17 cardenolides, cardenolide glucuronides and sulfates producing half-maximal inhibition of (Na+, K+)-membrane-ATPase from different organs and animal species were determined in vitro. In addition the concentrations that increased the contractility of guinea pig isolated papillary muscles to a particular level were investigated. Comparisons between ATPase-inhibiting and positive inotropic cardiac activities showed extensive parallelism: the correlation coefficients after log/log transformation were between 0.92 and 0.97. The same close correlations are found if dissociation constants of cardenolide receptor complexes and concentrations causing 86Rb-uptake inhibition in human erythrocytes are examined. The concentrations necessary for inhibition of (Na+, K+)-membrane-ATPase of the guinea pig heart and the concentrations required to achieve a defined positive inotropic effect in guinea pig papillary muscle showed a log/log correlation coefficient of 0.97 (P less than 0.001). In both tests the potencies covered more than three orders of magnitude. The results support Repke's hypothesis on the digitalis receptor.
D000818:Animals; D001921:Brain / Q000201:enzymology; D002298:Cardenolides / Q000494:pharmacology*; D002415:Cats; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology; D004912:Erythrocytes / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology* / Q000648:ultrastructure; D010210:Papillary Muscles / Q000201:enzymology; D012413:Rubidium / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D002298:Cardenolides; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium