Document Detail

Kinetic analysis of antagonist action at N-methyl-D-aspartic acid receptors. Two binding sites each for glutamate and glycine.
MedLine Citation:
PMID:  1710938     Owner:  NLM     Status:  MEDLINE    
Antagonism of glutamate-receptor responses activated by N-methyl-D-aspartic acid (NMDA) was studied using whole cell voltage clamp recording from mouse dissociated hippocampal neurons cultured for 10-15 d. The kinetics of onset of and recovery from NMDA receptor block during continuous application of NMDA together with either glycine, or L-alanine, were recorded in response to concentration jump application of NMDA- and glycine-binding site directed competitive antagonists, applied with a multibarrel flow pipe under conditions which allowed rapid solution changes around the cell less than 10 ms. Mathematical solutions for both one- and two-equivalent site models for competitive antagonism were determined according to the differential equations outlined by Colquhoun and Hawkes (1977. Proc. R. Soc. Lond. B. 199:231-262). The kinetics of action of D-CPP and D-AP5, NMDA binding site antagonists, and 7Cl-kynurenic acid, a glycine binding site antagonist, were examined for each model. For all these antagonists, the kinetics for the onset of and recovery from antagonism were better fit by the two-equivalent site model, which yielded antagonist microscopic kBoff/kBon values which closely approximated Ki values determined from analysis of equilibrium dose response curves. These results suggest that two molecules of NMDA and two molecules of glycine must bind to the NMDA receptor for activation of ion channel gating.
M Benveniste; M L Mayer
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biophysical journal     Volume:  59     ISSN:  0006-3495     ISO Abbreviation:  Biophys. J.     Publication Date:  1991 Mar 
Date Detail:
Created Date:  1991-07-23     Completed Date:  1991-07-23     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370626     Medline TA:  Biophys J     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  560-73     Citation Subset:  IM    
Unit of Neurophysiology and Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
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MeSH Terms
2-Amino-5-phosphonovalerate / pharmacology
Binding Sites
Biophysical Phenomena
Cells, Cultured
Glutamates / metabolism
Glutamic Acid
Glycine / metabolism
Hippocampus / metabolism
Ion Channels / metabolism
Kynurenic Acid / analogs & derivatives,  pharmacology
Models, Neurological
Piperazines / pharmacology
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors,  metabolism*
Reg. No./Substance:
0/Glutamates; 0/Ion Channels; 0/Piperazines; 0/Receptors, N-Methyl-D-Aspartate; 100828-16-8/3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; 18000-24-3/7-chlorokynurenic acid; 492-27-3/Kynurenic Acid; 56-40-6/Glycine; 56-86-0/Glutamic Acid; 76726-92-6/2-Amino-5-phosphonovalerate

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

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