| Quinolinate-induced cortical cholinergic damage: modulation by tryptophan metabolites. | |
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MedLine Citation:
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PMID: 2149296 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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) |
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Authors:
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K Jhamandas; R J Boegman; R J Beninger; M Bialik |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Brain research Volume: 529 ISSN: 0006-8993 ISO Abbreviation: Brain Res. Publication Date: 1990 Oct |
Date Detail:
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Created Date: 1991-03-19 Completed Date: 1991-03-19 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 185-91 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, Queen's University Kingston, Ont., Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3-Hydroxyanthranilic Acid
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pharmacology Acetylcholine / metabolism* Animals Brain / drug effects, metabolism, pathology* Cerebral Cortex / drug effects, metabolism, pathology* Kynurenic Acid / pharmacology* Male Neurotoxins / toxicity* Parietal Lobe / drug effects, metabolism, pathology Picolinic Acids / pharmacology* Potassium / pharmacology Quinolines / pharmacology* Quinolinic Acid Quinolinic Acids / toxicity* Rats Rats, Inbred Strains Tryptophan / analogs & derivatives |
| Chemical | |
Reg. No./Substance:
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0/Neurotoxins; 0/Picolinic Acids; 0/Quinolines; 0/Quinolinic Acids; 492-27-3/Kynurenic Acid; 51-84-3/Acetylcholine; 548-93-6/3-Hydroxyanthranilic Acid; 73-22-3/Tryptophan; 7440-09-7/Potassium; 89-00-9/Quinolinic Acid; 93-10-7/quinaldic acid; 98-98-6/picolinic acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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