Document Detail


Action of 4-amino-2-fluorobutanoic acid and other structural analogues on gamma-aminobutyric acid transport by channel catfish brain.
MedLine Citation:
PMID:  12670027     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in mammalian brain. The synaptic action of GABA is terminated by a sodium- and chloride-linked transport system. The GABA transporter is known as GAT and several isoforms have been identified. Many components of a GABA neurotransmitter system, including a GABA transport system, are present in channel catfish brain. Using a synaptosomal preparation of catfish brain, we examined the kinetics of inhibition of GABA transport by 4-amino-2-fluorobutanoic acid and several other structural analogues of GABA. The transport constant (Kt) for GABA uptake was 4.46 microM, and 4-amino-2-fluorobutanoic acid produced a noncompetitive type of inhibition (Ki = 12.5 microM). The most potent inhibitors were tiagabine (Ki = 0.23 microM) and (R,S)nipecotic acid (Ki = 2.2 microM), both of which exhibited competitive inhibition. Like 4-amino-2-fluorobutanoic acid, homo-beta-proline (Ki = 9.4 microM) inhibited noncompetitively. Other analogues exhibited competitive inhibition. These observations suggest that the GABA transport system in channel catfish is remarkably similar to that in mammalian brain.
Authors:
Glenda J Crites; Linda A Malizia; Godfrey Tunnicliff
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of basic and clinical physiology and pharmacology     Volume:  13     ISSN:  0792-6855     ISO Abbreviation:  J Basic Clin Physiol Pharmacol     Publication Date:  2002  
Date Detail:
Created Date:  2003-04-02     Completed Date:  2003-10-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9101750     Medline TA:  J Basic Clin Physiol Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  179-92     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Evansville, IN 47712, USA. gtunnic@iupui.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport, Active / drug effects
Brain Chemistry / drug effects*
Chlorides / metabolism
GABA Antagonists / pharmacology*
Ictaluridae / metabolism*
Nerve Tissue Proteins / metabolism
Sodium / metabolism,  pharmacology
Sodium Channels / drug effects,  metabolism
Temperature
gamma-Aminobutyric Acid / analogs & derivatives*,  metabolism*,  pharmacology*
Chemical
Reg. No./Substance:
0/4-amino-2-fluorobutanoic acid; 0/Chlorides; 0/GABA Antagonists; 0/Nerve Tissue Proteins; 0/Sodium Channels; 56-12-2/gamma-Aminobutyric Acid; 7440-23-5/Sodium

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


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