Since picolinic acid, a tryptophan metabolite yielded by the kynurenine pathway, selectively attenuates quinolinic and kainic acid excitotoxicity that is dependent on the presence of a glutamatergic afferent input, it was hypothesized that this agent may inhibit the presynaptic release of glutamate. Using superfused rat striatal slices, this study examined the potential of picolinic acid, and r...

In preceding reports from this laboratory, a-hydroxyanthranilic acid was shown to be converted to glutaric acid and COz by crude extracts of cat liver (l-3). Evidence was also presented that ol-amino-p-carboxymuconic e-semialdehyde, the primary oxidation product of 3-hydroxyanthranilic acid by the oxygenase (4), is an obligatory intermediate in this conversion (2,3). However, all previous exper...

Picolinic Acid is an endogenous metabolite of L-tryptophan (TRP) that has been reported to possess a wide range of neuroprotective, immunological, and anti-proliferative affects within the body. However the salient physiological function of this molecule is yet to be established. The synthesis of picolinic acid as a product of the kynurenine pathway (KP) suggests that, similar to other KP metab...

Picolinic acid, a catabolite of L-tryptophan, activates the transcription of the inducible nitric oxide synthase gene (iNOS) in IFN-gamma-treated murine macrophages. We performed functional studies on the 5' flanking region of the iNOS gene linked to a CAT reporter gene to identify the cis-acting element(s) responsible for the activation of iNOS transcription by picolinic acid. Transient transf...

Previous results suggest that the tryptophan metabolite, picolinic acid may have the unusual properties of antagonizing the neurotoxic but not the neuroexcitant effects of another tryptophan metabolite, quinolinic acid in the central nervous system. The present experiments tested this possibility utilizing behavioural and tyrosine hydroxylase immunohistochemical techniques. In the first series ...

Everted sacs of rat duodenum and ileum were used to study the effect of anions and organic ligands on the absorption of zinc. The uptake per unit weight of tissue was greater in duodenum than ileum, and it was influenced by the Zn concentration and pH of the incubation medium. The Zn uptake from inorganic salts in simple buffered medium varied in the order zinc sulphate greater than zinc chlori...

Certain products of tryptophan metabolism interact with excitatory amino acid receptors to produce or protect against excitotoxicity. In this study, the action of several tryptophan metabolites, yielded by the kynurenine pathway, on cortical cholinergic toxicity was evaluated following focal injection into the rat nucleus basalis magnocellularis (nbM). Metabolites were injected singly or in com...

The ability of prostaglandin El (PGE1) and cholera toxin to increase cyclic AMP levels is potentiated g-fold when normal rat kidney (NRK) cells are treated with picolinic acid or histidinol, or grown in isoleucine-deficient medium. The response to (-)-isoproterenol is increased a-fold in NRK cells treated with picolinic acid but not in cells subjected to isoleucine deprivation. The increase in ...

Picolinic acid, a pyridine monocarboxylic acid derived from tryptophan metabolism by the kynurenine pathway, was shown to block cortical cholinergic neurotoxicity induced by quinolinic acid (QUIN), a pyridine dicarboxylic acid yielded by the same pathway. This study examined the specificity of the anti-toxic effect of picolinic acid by comparing its effect with several structurally related mono...

The stability of new compounds with established anticonvulsant activity: picolinic acid 4-pyridyl-methylamide (Pic-4-PMA), cyclopentanecarboxylic acid benzylamide (Cpc-BZA), cycloheptanecarboxylic acid benzylamide (Chc-BZA), picolinic acid 2-fluoro-3-trifluoromethylbenzylamide (Pic-2F-3TFM-BZA), 2-chloronicotinic acid benzylamide (2-Cl-Na-BZA), 6-chloronicotinic acid benzylamide (6-Cl-Na-BZA) a...