Biomaterial Database

4-Chloro-3-hydroxyanthranilate inhibits quinolinate production in the rat hippocampus in vivo. 1994

J L Walsh, and H Q Wu, and U Ungerstedt, and R Schwarcz

Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228.

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010105	Oxygenases	Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.	Oxygenase
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005110	Extracellular Space	Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall.	Intercellular Space,Extracellular Spaces,Intercellular Spaces,Space, Extracellular,Space, Intercellular,Spaces, Extracellular,Spaces, Intercellular
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015095	3-Hydroxyanthranilic Acid	An oxidation product of tryptophan metabolism. It may be a free radical scavenger and a carcinogen.	3 Hydroxyanthranilic Acid,Acid, 3-Hydroxyanthranilic
D017207	Rats, Sprague-Dawley	A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.	Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017378	Quinolinic Acid	A metabolite of tryptophan with a possible role in neurodegenerative disorders. Elevated CSF levels of quinolinic acid are correlated with the severity of neuropsychological deficits in patients who have AIDS.	Quinolinate,Quinolinic Acid, Copper(2+) Salt,Quinolinic Acid, Disodium Salt,Quinolinic Acid, Strontium Salt
D017551	Microdialysis	A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.