Molecular Pharmacology, Vol 7, 46-51, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

On the Inhibition of (Na⁺ + K⁺)-Activated Adenosine Triphosphatase by Diisopropyl Fluorophosphate

¹ Department of Chemistry, University of Colorado, Boulder, Colorado 80302

The (Na⁺ + K⁺)-activated transport ATPase from guinea pig kidney cortex is inhibited in the presence of high concentrations of diisopropyl fluorophosphate (DFP) if Mg⁺⁺ is present, although the inhibition is caused not by DFP but by the fluoride released in its hydrolysis. Fluoride at 1 mM inhibits transport ATPase in a few minutes. The second-order rate constant for inhibition is 2.7 x 10² M^-1 min^-1. Mg⁺⁺ is necessary for the inhibition and K⁺ markedly increases the rate of inhibition, but Na⁺ is without effect. ATP prevents inhibition by fluoride, and fluoride inhibition can be reversed slowly. ¹⁴C-DFP even without Mg⁺⁺ rapidly labels one or more proteins in the ATPase preparation, but there is no evidence that these proteins are involved in the ATPase activity.