Document Detail

On the production and disposition of quinolinic acid in rat brain and liver slices.
MedLine Citation:
PMID:  8417142     Owner:  NLM     Status:  MEDLINE    
The de novo production and subsequent disposition of the endogenous excitotoxin quinolinic acid (QUIN) was investigated in vitro in tissue slices from rat brain and liver. Incubation of tissue with QUIN's immediate bioprecursor 3-hydroxyanthranilic acid (3-HANA) in oxygenated Krebs-Ringer buffer yielded measurable amounts of QUIN both in the tissue and in the incubation medium. Saturation was reached between 16 and 64 microM 3-HANA (166 pmol of QUIN formed per milligram of protein after a 60-min incubation with 64 microM 3-HANA). In the brain, more QUIN was recovered from the tissue than from the incubation medium at all time points examined (5 min to 4 h). In contrast, the tissue-to-medium ratio for QUIN in parallel experiments with hepatic slices was << 1. The disposition of newly synthesized QUIN was further elaborated in tissue slices that had been preincubated for 60 min with 64 microM 3-HANA. Subsequent incubation of brain tissue in fresh buffer revealed a steady but relatively slow efflux of QUIN from the cellular compartment, with > 30% remaining in the tissue after a 90-min incubation. Analogous experiments with liver slices showed that > 93% of newly synthesized QUIN had entered the extracellular compartment within 30 min. Striatal and nigral slices obtained 7 days after an intrastriatal ibotenic acid injection showed severalfold increases in QUIN production compared with control tissues, in all likelihood due to astrogliosis and associated large increases in 3-hydroxyanthranilic acid oxygenase activity. In addition, the apparent tissue-to-medium ratio was markedly reduced in striatal slices from lesioned animals.(ABSTRACT TRUNCATED AT 250 WORDS)
C Speciale; R Schwarcz
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  60     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  1993 Jan 
Date Detail:
Created Date:  1993-01-25     Completed Date:  1993-01-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  212-8     Citation Subset:  IM    
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228.
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MeSH Terms
3-Hydroxyanthranilic Acid / pharmacology
Brain / drug effects,  metabolism*
Ibotenic Acid / pharmacology
Liver / metabolism*
Quinolinic Acid / metabolism*
Rats, Sprague-Dawley
Grant Support
Reg. No./Substance:
2552-55-8/Ibotenic Acid; 548-93-6/3-Hydroxyanthranilic Acid; 89-00-9/Quinolinic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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