Effect of the convulsant methionine sulfoximine on the in vivo uptake and metabolism of D-methionine in rat brain.

D-methionine was administered intraperitoneally to rats in tracer (22.5 pmoles/kg) and large doses (4.7 mmoles/kg) and the brain levels of total (D + L) methionine, as well as of cysteine (+cystine) and glutathione were determined. The effect of co-administering the convulsant agent, L-methionine-DL-sulfoximine (MSO) was also examined. The administration of tracer doses of Cl2-D-methionine resulted in a doubling of total brain methionine within 4 hours post-injection, but only in a moderate increase of the levels of cysteine. When C14-D-methionine was used as tracer, the peak increase of the isotopic methionine pool and a peak accumulation of 0.35 "/o of the injected radioactivity were noted in the brain within 1.5 hours. When 4.7 mmoles/kg of D-methionine were administered, total brain methionine and cysteine increased by 4and 3-fold respectively, the former peaking a t 1.5 hr and the latter at 2.5 hr post-injection. The administration of MSO retarded the attainment of these peaks. I t could also be shown that while about 65% of the total brain methionine existed as the D-isomer 1.5 hr after its administration, only 46% was still present as the D-isomer 0.5 hr later. When MSO was administered simultaneously with D-methionine, the corresponding percentage values stood a t 70% a t 1.5 and at 2 hr. The results, therefore, suggest that even though D-methionine reaches the brain largely unchanged, its uptake and its conversion to the natural L-isomer may be inhibited by MSO under certain conditions and hence its conversion to cysteine retarded.