Sodium-potassium-activated adenosine triphosphatase of brain microsomes: modification of sodium inhibition by diphenylhydantoins

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Abstract
Effects of diphenylhydantoins on (Na+ + K+)-ATPase activity in rat and cat brain microsomes were studied. 5,5-diphenylhydantoin (DPH) in concentrations of 5-20 μg ml-1 produces an apparent stimulation of the rat brain (Na+ + K+)-activated ATPase of 55-65% in media containing 50 mM Na+, 0.15 mM K+, 3 mM Mg++, and 3 mM ATP. No effects are found on the Mg-ATPase. At constant K+ levels of 0.05 mmole/liter and 0.15 mmole/liter, increasing the Na+ concentration activates the enzyme similarly with and without DPH. However, Na+ concentrations greater than 5 mmoles/liter and 10 mmoles/liter, respectively, which are inhibitory in these low K+ media, produce less inhibition in the presence of DPH. In media containing 10 mM Na+, the K+ activation, on the other hand, is potentiated by DPH. In preparations from cat brain qualitatively similar results are obtained. No effect of DPH is seen on the inhibition produced by high K+ in low Na+ media. DPH produces an approximately constant apparent stimulation of 45% in the (Na+ + K+) increments when these ions are varied simultaneously at a fixed ratio of 150 Na+:1 K+ with cat brain extracts. 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH) has the same potency as DPH in reducing the Na+ inhibition at high Na:K ratios. The hydantoins appear to act by decreasing the Na+ inhibition that occurs at high Na:K ratios.