Effect of the convulsant methionine sulfoximine on thein vivo uptake and metabolism of d-methionine in rat brain

✍ Scribed by Ghittoni, Nora E. ;Sellinger, Otto Z.

• Publisher: John Wiley and Sons
• Year: 1971
• Tongue: English
• Weight: 906 KB
• Volume: 2
• Category: Article
• ISSN: 0022-3034
• DOI: 10.1002/neu.480020208

✦ Synopsis

Abstract

D‐methionine was administered intraperitoneally to rats in tracer (2–2.5 μmoles/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 C^12^‐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 C^14^‐D‐methionine was used as tracer, the peak increase of the isotopic methionine pool and a peak accumulation of 0.35% 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 4‐ and 3‐fold respectively, the former peaking at 1.5 hr and the latter at 2.5 hr post‐injection. The administration of MSO retarded the attainment of these peaks. It 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 at 70% at 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.