HPLC RIA ANALYSIS OF BIOACTIVE METHIONINE-ENKEPHALIN CONTENT IN THE SEIZURE-SUSCEPTIBLE E1 MOUSE-BRAIN/

We previously reported a deficit of methionine enkephalin-like immunor eactivity (ME-LI), in the cerebral cortex, septal area, hippocampus, a nd striatum and the abnormal metabolism of opioid peptides in the hipp ocampus and striatum of seizure-susceptible El mice, which are involve d in the pathogenesis of seizures. However, these findings suggest tha t the ME-LI does not necessarily reflect the bioactive methionine enke phalin (ME). Herein, we measured the biologically active peptide, ME e xcluding cross-reactive substances by using HPLC coupled with radioimm unoassay to clarify the abnormal function of enkephalinergic neurons i n the El mouse brain. The ME content in 25-day-old El mice that had no seizures was significantly decreased in the hippocampus and septal ar ea, as compared with corresponding regions in ddY mice (seizure-nonsus ceptible; the mother strain of El). At the age of 50 days when El mice displayed abortive seizures, this content in both stimulated El[s] an d nonstimulated El[ns] was significantly reduced in the septal area an d cerebral cortex. At the age of 150 days when El mice exhibit tonic-c lonic seizures, this content in both El[s] and El[ns] was significantl y reduced in the septal area, cerebral cortex and striatum. These find ings were generally compatible with our previous findings. This study further supports our hypothesis that a deficit of anticonvulsant endog enous ME, in the cerebral cortex, septal area, and hippocampus of seiz ure-susceptible El mice play an important role in the pathogenesis of seizures.