SNAP and SIN-1 increase brain production of kynurenic acid.
The influence of nitric oxide (NO) donors, S-nitroso-N-acetylpenicillamine (SNAP), and 3-morpholinosydnonimine (SIN-1), on the central production of an endogenous glutamate receptor antagonist, kynurenic acid, was evaluated in vitro. In cortical slices, SNAP and SIN-1 potently increased the extracellular concentration of kynurenic acid. A free radical scavenger, l-ascorbate reversed this effect. Neither SNAP nor SIN-1 altered the activity of kynurenic acid biosynthetic enzymes, kynurenine aminotransferases (KAT I and II). These data reveal a novel aspect of the brain response to studied herein NO donors and suggest that in the milieu containing NO-related free radicals the formation of kynurenic acid is enhanced.
Luchowski
Piotr
P
Department of Pharmacology, Skubiszewski Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
Urbanska
Ewa M
EM
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000378:metabolism*; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology*
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; D008981:Molsidomine; D007736:Kynurenic Acid; D001205:Ascorbic Acid