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.