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Phenytoin Dephosphorylates the Catalytic Subunit of the (Na + ,K + )‐ATPase in C57/BL Mice
Author(s) -
Guillaume Daniel,
Grisar Thierry,
DelgadoEscueta Antonio V.
Publication year - 1986
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1986.tb00696.x
Subject(s) - phosphorylation , chemistry , phenytoin , atpase , protein subunit , gel electrophoresis , sodium , oligomycin , enzyme , biophysics , biochemistry , biology , epilepsy , organic chemistry , neuroscience , gene
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 (∼50% at 10 −4 M ). When the conversion of E 1 ‐P to E 2 ‐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.