Possible role of increased brain methylation in methionine sulfoximine epileptogenesis: effects of administration of adenosine and homocysteine thiolactone.

An intraventricular pulse of [14COOH]L-methionine to mice pretreated with the convulsant L-methionine-dl-sulfoximine (MSO) resulted in significantly higher than control specific radioactivity values of cerebral [14COOH]L-methionine (Met), [14COOH]S-adenosyl-L-methionine (AdoMet) and [14COOH]S-adenosyl-L-homocysteine (AdoHcy). MSO administration (3 hr) also decreased brain steady-state levels of Met, AdoMet, and AdoHcy. Following an intraventricular pulse of [3H-methyl]L-methionine, the levels of [3H-methyl]phosphatidylmonomethylethanolamine and of membrane associated and soluble [3H-methyl]carboxylmethylated proteins were increased over corresponding saline-treated controls. The activity of cerebral histamine N-methyltransferase was also increased after MSO treatment. The administration of a combination of adenosine and homocysteine thiolactone to MSO-pretreated animals counteracted the MSO-induced decreases in brain Met, AdoMet, and AdoHcy as well as the increase in histamine N-methyltransferase activity. In addition, administration of adenosine together with homocysteine thiolactone decreased the incidence of, and increased the latency to MSO seizures, with the most effective anticonvulsant action occurring when cerebral AdoHcy levels were at their highest.