Neuroactive metabolites of L-tryptophan, serotonin and quinolinic acid, in striatal extracellular fluid. Effect of tryptophan loading.
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.
During
M J
MJ
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
Freese
A
A
Heyes
M P
MP
Swartz
K J
KJ
Markey
S P
SP
Roth
R H
RH
Martin
J B
JB
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
D011725:Pyridines; D011805:Quinolinic Acids; D012701:Serotonin; D014364:Tryptophan; D017378:Quinolinic Acid