Comparison of the affinity of human, beef and cat heart (Na+ + K+)-ATPase for different digitalis derivatives.
The potencies of eight digitalis derivatives, including two new derivatives of digitoxin, were determined on heart (Na+ + K+)-ATPase or erythrocytes from three digitalis-sensitive species, beef, cat and human. Three methods were used: inhibition of 3H-ouabain binding to give the dissociation constant (KD-value), or inhibition of (Na+ + K+)-ATPase activity or 86Rb+-uptake into human erythrocytes to give the IC50-values. The same order of potency was observed with all methods. The slopes of the concentration-response curves were similar for all compounds. For all compounds, the concentrations which inhibited 3H-ouabain binding by 50% caused about a 50% inhibition of (Na+ + K+)-ATPase activity. All three methods are suitable for determining the potency of new semisynthetic digitalis derivatives. The two new derivatives of digitoxin, 3"'-dehydrodigitoxin oxime and 3"'-dehydrodigitoxin methyloxime, were less potent than digitoxin but were of similar potency to ouabain.
D000818:Animals; D002415:Cats; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D004071:Digitalis Glycosides / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013045:Species Specificity
D004071:Digitalis Glycosides; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase