cgp-37849 and (3-nitrobenzoyl)alanine

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.

Topics: 2-Amino-5-phosphonovalerate; Aging; Alanine; Animals; Brain; Dextroamphetamine; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Glucose; Kynurenic Acid; Kynurenine 3-Monooxygenase; Male; Microdialysis; Mixed Function Oxygenases; N-Methylaspartate; Neurons; Pyruvates; Rats; Rats, Sprague-Dawley