Indolpyruvic acid administration increases the brain content of kynurenic acid. Is this a new avenue to modulate excitatory amino acid receptors in vivo?
The possibility of changing the tissue content of kynurenic acid (KYNA), a tryptophan metabolite which acts as an antagonist of the excitatory amino acid receptors, was investigated by measuring its concentration in the brain, blood, liver and kidney of rats using a specific method based on ion exchange chromatography and HPLC. The administration of tryptophan (TRP) or of its keto analogue, indolpyruvic acid (IPA) (50-500 mg/kg i.p.), significantly increased, in a dose-dependent manner, the content of KYNA in various organs, including the brain. The increased brain content of KYNA after IPA administration could not be completely explained by considering that IPA may be transaminated to TRP and that the enzymes leading from TRP to KYNA are known. An alternative pathway of KYNA synthesis from IPA was therefore proposed. These findings indicate that it is possible to change the brain content of an endogenous glutamate antagonist. This could be a new avenue to modulate in vivo excitatory amino acid receptors.
Russi
P
P
Department of Preclinical and Clinical Pharmacology, Firenze, Italy.
Carlà
V
V
Moroni
F
F
D000818:Animals; D001921:Brain / Q000378:metabolism*; D007211:Indoles / Q000502:physiology*; D007668:Kidney / Q000378:metabolism; D007736:Kynurenic Acid / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000378:metabolism; D014364:Tryptophan / Q000502:physiology*
D007211:Indoles; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; C008122:indol-3-yl pyruvic acid; D014364:Tryptophan; D007736:Kynurenic Acid; D011339:Probenecid