Phenytoin dephosphorylates the alpha(-) catalytic subunit of (Na+, K+)-ATPase. A study in mouse, cat and human brain.
Phenytoin, a potent antiepileptic drug, has been thought to stimulate Na+, K+ transport across cell membranes, but its influence on (Na+, K+)-ATPase activity remains highly controversial. We have investigated the effects of the drug on the phosphorylation level of (Na+, K+)-ATPase partially purified from mouse, cat and human brain. (Na+, K+)-ATPase catalytic subunits [alpha(+) and alpha(-)] were resolved by sodium dodecylsulfate polyacrylamide gel electrophoresis. Previous experiments had shown that phenytoin dephosphorylates the (Na+, K+)-ATPase catalytic subunit by +/- 50% in C57/BL mice. In the present study, we showed that phenytoin (10(-4) M) decreases the phosphorylation level of (Na+, K+)-ATPase catalytic subunit by the same value in cat and human cortex. Moreover, that effect is predominant on the alpha(-) subunit, thought to be the predominant enzymatic form in non-neuronal or glial cells. The results are thus favoring the hypothesis that phenytoin stimulates the brain (Na+, K+)-ATPase. They further suggest that phenytoin mainly activates the glial enzymatic form, providing central nervous system with an enhanced ability to regulate extracellular K+.
Guillaume
D
D
Molecular Neuroscience Laboratories, Reed Neurological Research Center, University of California, Los Angeles.
Grisar
T
T
Delgado-Escueta
A V
AV
Minet
A
A
Vergniolle-Burette
M
M
Bureau-Heeren
M
M
D000818:Animals; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008861:Microsomes / Q000201:enzymology; D008970:Molecular Weight; D010672:Phenytoin / Q000494:pharmacology*; D010766:Phosphorylation; D000254:Sodium-Potassium-Exchanging ATPase / Q000302:isolation & purification / Q000378:metabolism*
D010672:Phenytoin; D000254:Sodium-Potassium-Exchanging ATPase