Document Detail


Potentiation of metabotropic GABAB receptors by L-amino acids and dipeptides in rat neocortex.
MedLine Citation:
PMID:  12742517     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Selected neutral L-alpha-amino acids, and their dipeptides, were reversible, stereospecific, potentiators of GABA(B) receptor-mediated hyperpolarizing responses to baclofen (3-100 microM) in rat neocortical slices. These responses were sensitive to the GABA(B) receptor antagonist (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid (Sch50911) (30 microM). Most potent were L-Leu, L-Ile and L-Phe, as were the dipeptides L-Phe-Phe and L-Phe-Leu, and less potent were L-Met, L-Val, L-Cys, L-Cystine, L-Tyr, L-Thr, L-Arg and L-Ser. Inactive were L-Trp, L-His, L-Lys and L-Pro. These potentiators gave leftward shifts of the baclofen concentration-response curves with a Hill slope of 2, and a marked increase in the maximal hyperpolarizing responses. Selected L-amino acids and dipeptides are a class of naturally occurring GABA(B) potentiators, which may be allosteric modulators.
Authors:
David I B Kerr; Jennifer Ong
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  468     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-05-13     Completed Date:  2009-02-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  103-8     Citation Subset:  IM    
Affiliation:
Department of Anaesthesia and Intensive Care, The University of Adelaide, South Australia, Adelaide, Australia
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MeSH Terms
Descriptor/Qualifier:
Allosteric Regulation / drug effects
Amino Acids / pharmacology*
Animals
Baclofen / administration & dosage,  pharmacology*
Dipeptides / pharmacology*
Dose-Response Relationship, Drug
Drug Synergism
GABA Agonists / administration & dosage,  pharmacology
Male
Neocortex / drug effects,  metabolism
Rats
Rats, Sprague-Dawley
Receptors, GABA-B / agonists*
Stereoisomerism
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Dipeptides; 0/GABA Agonists; 0/Receptors, GABA-B; 1134-47-0/Baclofen

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


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