Neuroactive metabolises of L‐tryptophan, serotonin and quinolinic acid, in striatal extracellular fluid effect of tryptophan loading

FEBS Letters

Freese, Andrew²  Roth, Robert H.³  Heyes, Melvyn P.¹  During, Matthew J.³  Martin, Joseph B.²  Markey, Stanford P.¹  Swartz, Kenton J.² 

[1] Section of Analytical Biochemistry, Laboratory of Clinical Science, NIMH, Bethesda, MD 20892, USA;Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;Departments of Pharmacology and Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA

关键词: Tryptophan;    Quinolinic acid;    Hydroxytryptamine;    5-;    Microdialysis;    CNS;    central nervous system;    5-HT;    5-hydroxytryptamine;    serotonin;    5-HIAA;    5-hydroxyindoleacetic acid;    N-Me-D-Asp;    N-methyl-D-aspartate;    QUIN;    quinolinic acid;    KYNA;    kynurenic acid;    ECF;    extracellular fluid;   

DOI  :  10.1016/0014-5793(89)81387-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Extracellular fluid levels of the neurotoxin quinolinic acid in the corpus striatum of rats, measured by in vivo microdialysis, were increased in a dose-dependent manner following the intraperitoneal administration of tryptophan. The lowest dose of tryptophan (12.5 mg/kg), equivalent to about 5% of the normal daily intake, increased peak quinolinic acid levels nearly 3-fold. At higher doses of tryptophan (up to 250 mg/kg), concentrations of quinolinic acid increased over 200-fold and exceeded potentially neurotoxic levels (10 μM). In contrast, the increase in extracellular serotonin following even the highest tryptophan dose was small (less than 2-fold). These data indicate that quinolinic acid is present in them extracellular fluid where it may function as a neuromodulator and that it is very responsive to physiological changes in precursor availability.

【 授权许可】

Unknown