Quinolinic acid concentrations in striatal extracellular fluid reach potentially neurotoxic levels following systemic L-tryptophan loading.
Following a systemic tryptophan load, striatal extracellular fluid levels of quinolinic acid in the rat were quantified using intracerebral microdialysis. After an intraperitoneal dose of L-tryptophan (250 mg/kg), quinolinic acid levels in striatal perfusates increased by 230 fold. Peak concentrations of quinolinic acid exceeded 10(-5)M, a concentration previously shown to be neurotoxic in vitro. These results indicate that quinolinic acid is markedly precursor responsive and that its concentration in striatal extracellular fluid may reach neurotoxic levels following an acute tryptophan load.
During
M J
MJ
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
Heyes
M P
MP
Freese
A
A
Markey
S P
SP
Martin
J B
JB
Roth
R H
RH
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D011725:Pyridines / Q000378:metabolism*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism*
D011725:Pyridines; D011805:Quinolinic Acids; D014364:Tryptophan; D017378:Quinolinic Acid