Phenytoin dephosphorylates the catalytic subunit of the (Na+,K+)-ATPase in C57/BL mice.

Abstract:

:The effects of phenytoin, a potent antiepileptic drug, on the active transport of cations within membranes remain controversial. To assess the direct effects of phenytoin on the Na+,K+ pump, we studied the drug's influence on the phosphorylation of partially purified (Na+,K+)-ATPase from mouse brain. (Na+,K+)-ATPase subunits were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Phenytoin, in vitro, decreased net phosphorylation of the (Na+,K+)-ATPase catalytic subunit in a dose-dependent manner (approximately 50% at 10(-4) M). When the conversion of E1-P to E2-P, e.g., the two major phosphorylated conformational states of (Na+,K+)-ATPase, was blocked by oligomycin or N-ethylmaleimide, phenytoin had no effect. The results suggest that phenytoin acts on the phosphatasic component of the reaction cycle, decreasing the phosphorylation level of the enzyme.

journal_name

J Neurochem

authors

Guillaume D,Grisar T,Delgado-Escueta AV

doi

10.1111/j.1471-4159.1986.tb00696.x

subject

Has Abstract

pub_date

1986-09-01 00:00:00

pages

904-11

issue

3

eissn

0022-3042

issn

1471-4159

journal_volume

47

pub_type

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