Effects of kynurenine metabolites on the electrocorticographic activity in the rat.
We examined the effects of kynurenine metabolites administered into the right cerebroventricle (1 micromol) on the electrocorticogram (ECoG) of rats to establish the role of kynurenines on brain function. Kynurenine, anthranilic acid, quinaldic acid, xanthurenic acid or 8-hydroxyquinaldic acid showed no effect on ECoG throughout the recording period of 4 hours. 3-Hydroxykynurenine had a transient suppressive effect on the ECoG, while kynurenic acid caused a slight suppression of ECoG activity. 3-Hydroxyanthranilic acid (3-OH-An), a metabolite of 3-hydroxykynurenine, induced spike discharges with a long latency (60-230 min). 3-OH-An is thought to be metabolized to o-aminophenol, 3-methoxyanthranilic acid, quinolinic acid, 2-ketoadipic acid and picolinic acid. Among 3-OH-An metabolites, only o-aminophenol induced spike discharges several minutes after administration, lasting for 60 min. On the other hand, quinolinic acid suppressed ECoG, though 3-methoxyanthranilic acid, 2-ketoadipic acid and picolinic acid had no effects on ECoG. These electrocorticographic findings suggest that 3-OH-An may induce spike discharges after it is metabolized in the brain to o-aminophenol.
Yokoi
I
I
Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, Japan.
Nishijima
Y
Y
Uchida
A
A
Kabuto
H
H
Yamamoto
N
N
Ogawa
N
N
D015095:3-Hydroxyanthranilic Acid / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation; D004569:Electroencephalography / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D007276:Injections, Intraventricular; D007737:Kynurenine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016166:Free Radical Scavengers; D015095:3-Hydroxyanthranilic Acid; D007737:Kynurenine