| 4-Chloro-3-hydroxyanthranilate inhibits quinolinate production in the rat hippocampus in vivo. | |
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MedLine Citation:
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PMID: 8186995 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Quinolinic acid (QUIN) is a potential pathogen in a variety of excitotoxic and neuroviral brain diseases. In the present study, the ability of the QUIN synthesis inhibitor 4-chloro-3-hydroxyanthranilic acid to attenuate the production of QUIN was assessed in the hippocampus of awake rats. To this end, QUIN's immediate bioprecursor 3-hydroxyanthranilic acid (30 microM) was applied through a microdialysis probe, and QUIN production was monitored hourly in the perfusate. After 3 h, 4-chloro-3-hydroxyanthranilic acid (3 microM-3 mM) was included in the perfusion medium, and dialysis was continued for another 3 h. The drug caused dose-dependent inhibition of QUIN neosynthesis, with an apparent IC50 value of 32 microM. Discontinuation of drug administration, with continued perfusion of 3-hydroxyanthranilic acid, revealed that the drug effect was reversible. Intravenous application of 4-chloro-3-hydroxyanthranilic acid (14 mg/kg) resulted in a significant decrease in extracellular QUIN, reaching a nadir of 67% of saline-treated controls after 3 h. The data indicate that both intracerebral and systemic administration of 4-chloro-3-hydroxyanthranilic acid effectively interferes with QUIN production in the rat brain. The results suggest that QUIN synthesis inhibitors such as 4-chloro-3-hydroxyanthranilic acid may become of value in brain diseases that are caused by hyperphysiological quantities of QUIN. |
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Authors:
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J L Walsh; H Q Wu; U Ungerstedt; R Schwarcz |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Brain research bulletin Volume: 33 ISSN: 0361-9230 ISO Abbreviation: Brain Res. Bull. Publication Date: 1994 |
Date Detail:
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Created Date: 1994-06-21 Completed Date: 1994-06-21 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7605818 Medline TA: Brain Res Bull Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 513-6 Citation Subset: IM |
Affiliation:
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Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3-Hydroxyanthranilate 3,4-Dioxygenase 3-Hydroxyanthranilic Acid / analogs & derivatives*, pharmacology Animals Dioxygenases* Dose-Response Relationship, Drug Extracellular Space / metabolism Hippocampus / drug effects, metabolism* Male Microdialysis Oxygenases / antagonists & inhibitors Quinolinic Acid / metabolism* Rats Rats, Sprague-Dawley |
| Grant Support | |
ID/Acronym/Agency:
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NS 16102/NS/NINDS NIH HHS; NS 28236/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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23219-33-2/4-chloro-3-hydroxyanthranilic acid; 548-93-6/3-Hydroxyanthranilic Acid; 89-00-9/Quinolinic Acid; EC 1.13.-/Oxygenases; EC 1.13.11.-/Dioxygenases; EC 1.13.11.6/3-Hydroxyanthranilate 3,4-Dioxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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