TY - JOUR T1 - Studies on the Interaction of Ouabain and Other Cardioactive Steroids with Sodium-Potassium-Activated Adenosine Triphosphatase JF - Molecular Pharmacology JO - Mol Pharmacol SP - 324 LP - 336 VL - 4 IS - 4 AU - R. W. ALBERS AU - G. J. KOVAL AU - G. J. SIEGEL Y1 - 1968/07/01 UR - http://molpharm.aspetjournals.org/content/4/4/324.abstract N2 - The combination of ouabain with (Na+ + K+)-ATPase is essentially irreversible at physiological temperature and pH. The rate of inhibition of the enzyme by different cardioactive steroids varies widely. The amount of steroid bound parallels the inhibition of enzyme activity. Mg2+, Na+, K+, nucleotides, and orthophosphate markedly influence the rate of interaction. In the presence of nucleotides, the rate is accelerated by Mg2+ and Na+ and retarded by K+. In the presence of orthophosphate, Mg2+ increases, K+ slows, and Na+ markedly decreases the rate of interaction. The ratio of ouabain binding to Na+-dependent phosphorylation is 0.50 for Electrophorus electric organ ATPase. In contrast to the native enzyme, the ouabain-treated enzyme rapidly incorporates orthophosphate. Cardioactive steroids appear to inhibit (Na+ + K+)-ATPase by reducing the difference between the conformational energies ot the phosphorylated and nonphosphorylated forms of the enzyme. ER -