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

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 mug 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.