Modulation of quinolinic and kynurenic acid content in the rat brain: effects of endotoxins and nicotinylalanine.
Quinolinic acid, an endogenous excitotoxin, and kynurenic acid, an antagonist of excitatory amino acid receptors, are believed to be synthesized from tryptophan after the opening of the indole ring. They were measured in the rat brain and other organs using gas chromatography-mass spectrometry or HPLC. The enzyme indoleamine 2,3-dioxygenase, capable of cleaving the indole ring of tryptophan, was induced by administering bacterial endotoxins to rats, which significantly increased the brain content of both quinolinic and kynurenic acids. Nicotinylalanine, an analogue of kynurenine, inhibited this endotoxin-induced accumulation of quinolinic acid while potentiating the accumulation of kynurenic acid. The possibility of significantly increasing brain concentrations of kynurenic acid without a concomitant increase in quinolinic acid may provide a useful approach for studying the role of these electrophysiologically active tryptophan metabolites in brain function and preventing the possible toxic actions of abnormal synthesis of quinolinic acid.
Moroni
F
F
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Russi
P
P
Gallo-Mezo
M A
MA
Moneti
G
G
Pellicciari
R
R
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D008401:Gas Chromatography-Mass Spectrometry; D007668:Kidney / Q000378:metabolism; D007736:Kynurenic Acid / Q000097:blood / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D008959:Models, Neurological; D009525:Niacin / Q000031:analogs & derivatives* / Q000494:pharmacology; D009928:Organ Specificity; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004731:Endotoxins; D008070:Lipopolysaccharides; D011805:Quinolinic Acids; C071261:nicotinylalanine; D009525:Niacin; D017378:Quinolinic Acid; D007736:Kynurenic Acid; D000409:Alanine