Molecular Pharmacology, Vol 11, 166-173, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Antibiotics as Tools for Metabolic Studies XVIII. Inhibition of Sodium- and Potassium-Dependent Adenosine Triphosphatase

¹ Institute for Enzyme Research and Department of Biochemistry, University of Wisconsin, Madison, Wisconsin

Antibiotics that inhibit oxidative phosphorylation or the uncoupler-induced mitochondrial ATPase activity were tested as inhibitors of rat brain (Na⁺ + K⁺)-dependent ATPase. Peliomycin, oligomycin B, and rutamycin in micromolar concentrations were found to be potent inhibitors of the (Na⁺ + K⁺)-dependent ATPase. At millimolar concentrations venturicidin X, venturicidin, and, to a lesser extent, ossamycin were also inhibitory. Even at high concentrations, aurovertin, A20668B (leucinostatin), and A23871 (efrastatin) were not inhibitory. All the antibiotics that were effective inhibitors of the over-all reaction had negligible effects on the K⁺-dependent phosphatase activity in the absence of Na⁺, with p-nitrophenyl phosphate as substrate. Inhibition by antibiotics could be relieved by washing. The Mg⁺⁺ concentration was found to be important in regulating the degree of inhibition. The ATP-ADP exchange reaction characteristic of the (Na⁺ + K⁺)-dependent activity was stimulated by the inhibitors. The pattern of inhibition by the antibiotics tested suggests that the mitochondrial uncoupler-induced ATPase and the (Na⁺ + K⁺)-dependent ATPase possess some mechanistic similarity.