Document Detail


Novel parent structures for inhibitors of the murine GABA transporters mGAT3 and mGAT4.
MedLine Citation:
PMID:  16111674     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Searching for potent and subtype selective parent structures of the murine gamma-aminobutyric acid (GABA) transporter subtypes mGAT3 and mGAT4 a series of amino acids was characterised in a uniform [3H]GABA uptake test system based on transiently expressed mGAT1-4. From several potent inhibitors showing IC50 values at mGAT3 and mGAT4 in the low microM range cis-4-aminocrotonic acid and (RS)-2,3-diaminopropionic acid turned out to be most subtype selective for these transporters. With (RS)-isoserine--a compound unknown as GAT inhibitor until now--one of the most potent amino acids selectively inhibiting mGAT3 and mGAT4 was found. Furthermore, (2-amino-1,3-thiazol-4-yl)acetic acid was identified as the first parent structure exhibiting a clear, though still moderate, selective inhibition of GABA uptake at mGAT3.
Authors:
Andrea Kragler; Georg Höfner; Klaus T Wanner
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  519     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-05     Completed Date:  2005-11-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  43-7     Citation Subset:  IM    
Affiliation:
Department Pharmazie-Zentrum für Pharmaforschung-Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, D-81377 München, Germany.
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MeSH Terms
Descriptor/Qualifier:
Acetic Acids / chemistry,  pharmacology
Animals
COS Cells
Cell Line
Cercopithecus aethiops
Dose-Response Relationship, Drug
GABA Plasma Membrane Transport Proteins
Guanidines / chemistry,  pharmacology
Humans
Membrane Transport Modulators*
Membrane Transport Proteins / antagonists & inhibitors*,  genetics,  metabolism
Mice
Molecular Structure
Neurotransmitter Uptake Inhibitors / chemistry,  pharmacology*
Plasmids / genetics
Propionic Acids / chemistry,  pharmacology
Serine / analogs & derivatives,  chemistry,  pharmacology
Structure-Activity Relationship
Thiazoles / chemistry,  pharmacology
Transfection
Tritium
beta-Alanine / analogs & derivatives,  chemistry,  pharmacology
gamma-Aminobutyric Acid / metabolism
Chemical
Reg. No./Substance:
0/(2-amino-1,3-thiazol-4-yl)acetic acid; 0/Acetic Acids; 0/GABA Plasma Membrane Transport Proteins; 0/Gabt4 protein, mouse; 0/Guanidines; 0/Membrane Transport Modulators; 0/Membrane Transport Proteins; 0/Neurotransmitter Uptake Inhibitors; 0/Propionic Acids; 0/Slc6a12 protein, mouse; 0/Slc6a13 protein, mouse; 0/Thiazoles; 10028-17-8/Tritium; 107-95-9/beta-Alanine; 353-09-3/guanidinopropionic acid; 515-94-6/2,3-diaminopropionic acid; 56-12-2/gamma-Aminobutyric Acid; 56-45-1/Serine; 565-71-9/isoserine

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


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