title: Modulation and function of kynurenic acid in the immature rat brain.
abstract: Using in vivo and in vitro paradigms, the regulation and function of the brain metabolite kynurenic acid (KYNA) was examined in rats on postnatal days (PND) 7 and 14. As shown previously in adult rats, glucose removal and d-amphetamine (d-Amph) administration caused decreases in KYNA formation, while exposure to pyruvate up-regulated KYNA synthesis. The effect of glucose deprivation was substantially blunted in immature animals. In PND 14 rats, d-Amph pre-treatment exacerbated the excitotoxic effects of an intrastriatal N-methyl-D-aspartate (NMDA) injection. This potentiation was prevented by m-nitrobenzoylalanine, a kynurenine 3-hydroxylase inhibitor that also antagonized the KYNA reduction caused by d-Amph. These and additional experiments with the competitive NMDA receptor antagonist CGP 40116 indicate the existence of a functionally significant, novel high-affinity receptor for KYNA in the brain.
authors.affiliation: Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228, USA. rschwarc@umaryland.edu
authors.forename: R
authors.initials: R
authors.lastname: Schwarcz
authors.forename: G
authors.initials: G
authors.lastname: Ceresoli-Borroni
authors.forename: H Q
authors.initials: HQ
authors.lastname: Wu
authors.forename: A
authors.initials: A
authors.lastname: Rassoulpour
authors.forename: B
authors.initials: B
authors.lastname: Poeggeler
authors.forename: P S
authors.initials: PS
authors.lastname: Hodgkins
authors.forename: P
authors.initials: P
authors.lastname: Guidetti
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000375:Aging / Q000378:metabolism; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D003913:Dextroamphetamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007736:Kynurenic Acid / Q000378:metabolism*; D050601:Kynurenine 3-Monooxygenase; D008297:Male; D017551:Microdialysis; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011773:Pyruvates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D011773:Pyruvates; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; C086214:(3-nitrobenzoyl)alanine; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D006899:Mixed Function Oxygenases; D050601:Kynurenine 3-Monooxygenase; D007736:Kynurenic Acid; D005947:Glucose; D000409:Alanine; D003913:Dextroamphetamine