Evidence that diphenylhydantoin does not affect adenosine triphosphatases from brain.

The effects of diphenylhydantoin on brain sodium- and potassium-dependent adenosine triphosphatase (NaK ATPase), p-nitrophenylphosphatase and the calcium-dependent adenosine triphosphatase (Ca ATPase) were examined. The results indicated that: (1) diphenylhydantoin did not stimulate the NaK ATPase of beef brain sodium iodide-treated microsomes or rat brain synaptosomes at nonsaturating or saturating levels of sodium and potassium: (2) the apparent stimulation by diphenylhydantoin under high sodium: potassium ratios reported by other workers can be explained by a potassium contamination in the diphenylhydantoin; (3) diphenylhydantoin did not alter the Michaelis constant for ATP for the NaK ATPase; (4) diphenylhydantoin did not slowly interact with or alter the NaK ATPase; (5) diphenylhydantoin did not alter the calcium inhibition of the enzyme and (6) diphenylhydantoin did not alter the p-nitrophenylphosphatase or Ca ATPase. Based on these considerations, diphenylhydantoin must be exerting its pharmacological effect by altering a membrane constituent other than the NaK ATPase.