Phenytoin dephosphorylates the catalytic subunit of the (Na+,K+)-ATPase in C57/BL mice.
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.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D005033:Ethylmaleimide / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009840:Oligomycins / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology*; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D011487:Protein Conformation; D012964:Sodium / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000302:isolation & purification / Q000378:metabolism*
D009840:Oligomycins; D010672:Phenytoin; D000244:Adenosine Diphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D005033:Ethylmaleimide; D011188:Potassium