Phenytoin Dephosphorylates the Catalytic Subunit of the (Na+,K+)-ATPase in C57/BL Mice |
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| Authors: | Daniel Guillaume Thierry Grisar† Antonio V Delgado-Escueta |
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| Institution: | Molecular Neuroscience Laboratories, Comprehensive Epilepsy Program, Reed Neurological Research Center, University of California at Los Angeles, Los Angeles, California, U.S.A.;Institut de Biochimie Générale et Comparée, Laboratoire de Neurochimie, Universitéde Liège, Liège, Belgium |
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| 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. |
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| Keywords: | Phenytoin (Na+ K+)-ATPase C57/BL mice |
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