Binding of digitalis derivatives to beef, cat and human cardiac (Na+ + K+)-ATPase. Affinity and kinetic constants.
We have measured the potency of 17 digitalis derivatives on cardiac (Na+ + K+)-ATPase from the digitalis-sensitive species, beef, cat and human. The potencies are given as the dissociation constant (KD-value) calculated from the concentration of unlabelled compound which inhibited 3H-ouabain binding by 50%, or from Scatchard or Woolf analyses. KD-values calculated by these independent methods were similar. As previously noted, structure-activity relationship (SAR) studies show that the binding of the whole molecule is necessary for optimal potency. The 3H-labelled derivatives of five of these compounds were used to measure the association and dissociation rate constants with cardiac (Na+ + K+)-ATPase. The rate constants for cat and human cardiac (Na+ + K+)-ATPase were very similar. Further, KD-values on cat and human cardiac (Na+ + K+)-ATPase for the 17 compounds tested showed a close correlation (r greater than 0.99), indicating that the cat heart is a suitable model for digitalis effects on the human heart.
D000818:Animals; D001665:Binding Sites; D002415:Cats; D002417:Cattle; D004071:Digitalis Glycosides / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013045:Species Specificity; D014316:Tritium
D004071:Digitalis Glycosides; D014316:Tritium; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase