PT  - JOURNAL ARTICLE
AU  - JOHN B. SUSA
AU  - HENRY A. LARDY
TI  - Antibiotics as Tools for Metabolic Studies XVIII. Inhibition of Sodium- and Potassium-Dependent Adenosine Triphosphatase
DP  - 1975 Mar 01
TA  - Molecular Pharmacology
PG  - 166--173
VI  - 11
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/11/2/166.short
4100  - http://molpharm.aspetjournals.org/content/11/2/166.full
SO  - Mol Pharmacol1975 Mar 01; 11
AB  - 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.