Glycogen content and fructose-1, 6-biphosphatase activity in methionine sulfoximine epileptogenic mouse brain and liver after protein synthesis inhibition.

Mice given intraperitoneal injections of methionine sulfoximine (MSO) (100 mg/kg body weight) showed tonic-clonic seizures 7 to 8 h later. The protein synthesis inhibitors actinomycin D and cycloheximide, when combined with MSO delayed the onset of seizures. Methionine completely abolished the convulsions and metyrapone delayed them for some hours. Twenty-four h after the administration of the convulsant, the activity of the gluconeogenic enzyme, fructose-1, 6-biphosphatase (FBPase), and the glycogen content were determined in different areas of the brain. MSO induced an increase in both FBPase activity and glycogen content. These effects were antagonized by the inhibitors of protein synthesis. Metyrapone partly inhibited MSO-induced increases of FBPase activity and glycogen content whereas methionine completely abolished them. MSO decreased glycogen content in liver but had no effect on blood glucose level 24 h after its administration. These findings suggested that in MSO epileptogenic brain, glycogen accumulation may proceed from an enhanced gluconeogenesis.