Effect of the convulsant methionine sulfoximine on thein vivouptake and metabolism of d‐methionine in rat brain
作者:
Nora E. Ghittoni,
Otto Z. Sellinger,
期刊:
Journal of Neurobiology
(WILEY Available online 1971)
卷期:
Volume 2,
issue 2
页码: 153-168
ISSN:0022-3034
年代: 1971
DOI:10.1002/neu.480020208
出版商: Wiley Subscription Services, Inc., A Wiley Company
数据来源: WILEY
摘要:
AbstractD‐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 C12‐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% 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 1.5andat 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 h
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