The in vivo and in vitro effect of diphenylhydantoin and phenobarbitone on K+ activated phosphohydrolase and (Na+, K+)-activated ATPase in particulate membrane fractions from rat brain.

Abstract

Abstract The effect of diphenylhydantoin and phenobarbitone on a K+-activated phosphohydrolase, hydrolysing the artificial substrates p-nitrophenylphosphate and acetylphosphate, and (Na+, K+)-activated ATPase in particulate membrane fractions from rat brain, has been studied. Diphenylhydantoin was given orally over 20 weeks without any effect on these enzymic activities, whereas orally phenobarbitone significantly decreased the enzymic activities in the particulate membrane fractions containing synaptosomes, nerve endings and microsomes. In vitro, diphenylhydantoin inhibited the enzymic activities in the synaptosomal membrane fraction, but phenobarbitone did not. Several possibilities for the in vivo action of diphenylhydantoin are outlined; these are mainly concerned with a blocking of the passive movement of sodium into the cell. The in vivo effect of phenobarbitone is possibly a secondary pharmacological effect interfering with the utilization of ATP either directly or indirectly by a depression of some energy dependent processes such as protein synthesis.