Modulation and function of kynurenic acid in the immature rat brain.
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.
Schwarcz
R
R
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228, USA. rschwarc@umaryland.edu
Ceresoli-Borroni
G
G
Wu
H Q
HQ
Rassoulpour
A
A
Poeggeler
B
B
Hodgkins
P S
PS
Guidetti
P
P
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
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