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Neuroactive metabolises of L‐tryptophan, serotonin and quinolinic acid, in striatal extracellular fluid effect of tryptophan loading
Author(s) -
During Matthew J.,
Freese Andrew,
Heyes Melvyn P.,
Swartz Kenton J.,
Markey Stanford P.,
Roth Robert H.,
Martin Joseph B.
Publication year - 1989
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(89)81387-0
Subject(s) - quinolinic acid , microdialysis , tryptophan , neurotoxin , serotonin , extracellular , chemistry , extracellular fluid , striatum , endocrinology , medicine , pharmacology , biochemistry , biology , amino acid , dopamine , receptor
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.