ENDOGENOUS METHIONINE-ENKEPHALIN MAY PLAY AN ANTICONVULSANT ROLE IN THE SEIZURE-SUSCEPTIBLE E1 MOUSE

After the intracisternal injection of three protease inhibitors which prevent the degradation of methionine enkephalin (amastatin, Des-Pro2- bradykinin, and phosphoramidon) and a mixture of these protease inhibi tors, we investigated the effect on convulsive seizures in the seizure -susceptible El mouse. We also measured the cerebral methionine enkeph alin content by high-performance liquid chromatography coupled with ra dioimmunoassay. Protease inhibitors significantly decreased both the i ncidence of seizures and the seizure score in El mice in a dose-depend ent manner. This anticonvulsant effect was reversed by naloxone (2 mg/ kg, sc). The cerebral methionine enkephalin content increased signific antly after the administration of protease inhibitors in comparison wi th saline injection. These findings suggest that it was not protease i nhibitors but instead increase of endogenous methionine enkephalin tha t reduced the incidence of seizures and the seizure score in El mice. Together with our previous data, the present findings support our hypo thesis that a deficit in anticonvulsant endogenous methionine enkephal in is involved in the pathogenesis of seizures in the El mouse.