title: Neuroactive metabolites of L-tryptophan, serotonin and quinolinic acid, in striatal extracellular fluid. Effect of tryptophan loading.
abstract: 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 microM). 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 the extracellular fluid where it may function as a neuromodulator and that it is very responsive to physiological changes in precursor availability.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
authors.forename: M J
authors.initials: MJ
authors.lastname: During
authors.forename: A
authors.initials: A
authors.lastname: Freese
authors.forename: M P
authors.initials: MP
authors.lastname: Heyes
authors.forename: K J
authors.initials: KJ
authors.lastname: Swartz
authors.forename: S P
authors.initials: SP
authors.lastname: Markey
authors.forename: R H
authors.initials: RH
authors.lastname: Roth
authors.forename: J B
authors.initials: JB
authors.lastname: Martin
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011725:Pyridines / Q000378:metabolism*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D011725:Pyridines; D011805:Quinolinic Acids; D012701:Serotonin; D014364:Tryptophan; D017378:Quinolinic Acid