TY - JOUR T1 - Effects of Oligomycin on the (Na<sup>+</sup> + K<sup>+</sup>)-Dependent Adenosine Triphosphatase JF - Molecular Pharmacology JO - Mol Pharmacol SP - 238 LP - 246 VL - 7 IS - 3 AU - JOSEPH D. ROBINSON Y1 - 1971/05/01 UR - http://molpharm.aspetjournals.org/content/7/3/238.abstract N2 - Oligomycin inhibited a rat brain (Na+ + K+)-dependent ATPase (ATP phosphohydrolase, EC 3.6.1.3) preparation, but the inhibition was incomplete even at high oligomycin concentrations, and Dixon plots were concave downward. Inhibition increased as the incubation temperature was lowered. Elevated MgCl2 concentrations antagonized the inhibition, and relative inhibition was less at low (1 µM) than at high (1-3 mM) ATP concentrations. In the presence of ouabain, which also inhibited the enzyme, the relative efficacy of oligomycin decreased. Oligomycin influenced the kinetics of cation activation, diminishing Vmax and n (the slope of the Hill plot, an index of cooperativity) for both NaCl and KCl, and also reducing K0.5 (the concentration for half-maximal activation) for NaCl. Inhibition of the associated K+-dependent phosphatase activity could be demonstrated in the presence of NaCl, and oligomycin reduced Vmax and n for KCl activation in this case also. The data suggest that oligomycin decreases ATPase activity by affecting the equilibria between alternative allosteric forms of the enzyme, oligomycin favoring a form with a lower Vmax and a higher Q10, and with n for cation activation near 1.0; this shift in equilibria would be opposed by MgCl2 and temperature. It is proposed that both forms, reminiscent of E1 and E2, catalyze (Na+ + K+)-dependent hydrolysis and cation transport, since inhibition of transport by oligomycin is also reported to be incomplete. ACKNOWLEDGMENTS The careful technical assistance of Mr. Ronald Olmstead and Miss Mary Neville is gratefully acknowledged. ER -