Milacemide stimulates deficient glial Na+, K(+)-ATPase in freezing-induced epileptogenic cortex of cats.
We investigated the influence of milacemide, a glycinamide derivative with putative antiepileptic activity, on the K(+)-activation of Na+,K(+)-ATPase in bulk isolated glial cells and synaptosomes of control and epileptogenic cortex of cats with a chronic freeze lesion. In the primary and secondary epileptic foci of non-treated animals, glial Na+,K(+)-ATPase lost its physiological K(+)-activation, while the synaptosomal enzyme was unchanged. These data reproduced previous work done on the kinetic measurement of the enzymic activities. In treated animals (500 mg/kg milacemide given orally for 2 weeks after the freeze lesion), the glial enzyme showed a normal K(+)-activation in the epileptic foci. These results confirm the existence of an abnormal glial Na+,K(+)-ATPase in cold-induced focal epilepsy and suggest that the antiepileptic activity of milacemide might be secondary to an activation of glial Na+,K(+)-ATPase, contributing to antagonize ictal transformation and seizure spread.
Laschet
J
J
Laboratory of Biochemistry, C.H.U., University of Liège, Belgium.
Guillaume
D
D
Vergniolle-Burette
M
M
Grisar
T
T
D000081:Acetamides / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D004827:Epilepsy / Q000201:enzymology* / Q000503:physiopathology; D005615:Freezing; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology
D000081:Acetamides; D000927:Anticonvulsants; C039332:milacemide; D000254:Sodium-Potassium-Exchanging ATPase