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• W1998974416 abstract "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 combination with a fixed dose of quinolinic acid (QUIN). Cholinergic toxicity, or protection against it, was evaluated by measurements of choline acetyltransferase (ChAT) activity or potassium-evoked release of [3H]acetylcholine [( 3H]ACh) from slices of the frontoparietal cortex, from the injected and uninjected sides. Focal injections of QUIN and 3-hydroxyanthranilic, but not kynurenic, picolinic, quinaldic or anthranilic acid, produced a dose-related decrease in ChAT activity, with QUIN being more potent. Kynurenic, picolinic, quinaldic and anthranilic acid, co-injected into the nbM with QUIN (120 nmol), produced dose-related antagonism of the neurotoxicity associated with QUIN alone. Picolinic acid also prevented the reduction in cortical [3H]ACh release induced by injections of QUIN. Kynurenic and picolinic acid produced a complete blockade of QUIN's effect on cortical ChAT activity, while quinaldic and anthranilic acid produced a partial blockade. The order of effectiveness against QUIN was kynurenic greater than picolinic greater than quinalidic or anthranilic acid. Evaluation of thin sections following Cresyl violet staining indicated that injections of QUIN produced neuronal loss and glial proliferation, while co-injections of picolinic or quinaldic acid with QUIN protected neurons. These findings show that several tryptophan metabolites have the potential to either produce or antagonize cholinergic toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)" @default.
• W1998974416 created "2016-06-24" @default.
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• W1998974416 date "1990-10-01" @default.
• W1998974416 modified "2023-10-16" @default.
• W1998974416 title "Quinolinate-induced cortical cholinergic damage: modulation by tryptophan metabolites" @default.
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• W1998974416 doi "https://doi.org/10.1016/0006-8993(90)90826-w" @default.
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