Effect of methionine and methionine sulphoximine on rat brain S-adenosyl methionine levels.

Rat brain SAM levels were markedly increased after methionine administration, whereas the convulsant, L-methionine-dl-sulphoximine (MSO), produced a 35 per cent decrease in whole brain content of S-adenosyl-L-methionine (SAM). When methionine was given in combination with MSO, SAM levels were not decreased. Studies on the regional distribution of SAM revealed only a small variation between regions (from 24 nmol/g in midbrain to 493 nmol/g in striatum). SAM levels were reduced by about 50 per cent in the cerebellum, striatum, cortex and hippocampus 3 and 6 h after MSO. It is proposed that abberant cerebral methylation processes may be involved in the genesis of the MSO seizure. THE USE of the convulsant, methionine sulphoximine (MSO), to study seizure mechanisms is advantageous in that its rather long preconvulsive latency period (3 6 h) (REINER et al., 1950) allows one to follow the course of specific cellular and metabolic alterations resulting from its administration. Previous studies (LODIN & KOLOUSEK, 1958; LAMAR & SELLINGER, 1965; SELLINGER et al., 1970) have demonstrated that L-methionine administered concurrently with MSO in a 5 : 1 molar ratio markedly reduces the incidence and severity of seizures. The importance of S-adenosyl methionine (SAM) as a methyl donor (LDMBARDINI & TALALAY, 1971), the structural similarities between MSO, methionine and SAM and the fact that both BALDESSARINI (1966) and SALVATORE et al. (1971) reported that methionine administration increased SAM levels in rat and rabbit brain, respectively, led us to investigate the effect of MSO and methionine on SAM levels in rat whole brain and brain regions. MATERIALS AND METHODS