Hypermethylation in the MSO-epileptogenic brain: Reversal by dilantin or phenobarbital
Administration of the convulsant L-methionine-d, l-sulfoximine (MSO) has been shown to decrease the cerebral levels of the biologic methyl donor S-adenosyl-L-methionine (AdoMet) (Schatz and Sellinger, 1975a) as well as its demethylated product S-adenosyl-L-homocysteine (AdoHcy) (Schatz et al., 1977). These changes appear to be due to an increase in cerebral transmethylation flux as evidenced by an increase in histamine methylation both in vitro (Schatz and Sellinger, 1975b) and in vivo (Schatz et al., 1978), as well as an increase in protein carboxy- and phospholipid methylation in vivo (Schatz et al., 1981a). In vivo elevation of AdoHcy by co-administration of equimolar concentrations of adenosine (Ado) and homocysteine (Hcy) resulted in a decrease in cerebral histamine, phospholipid and protein carboxymethylation (PCM) (Schatz et al., 1981b,c). Administration of Ado+Hcy also prevents, at least partially, some of the MSO-induced increases in methylation and protects against MSO seizures (Schatz et al., 1981a). In view of these findings we investigated the effects of the clinical anticonvulsants Dilantin (DPH) and phenobarbital (PB) on cerebral transmethylation and MSO seizures.
KeywordsAdenosine Histamine Methionine Dilantin Homocysteine
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