Document Detail


Receptor activation by two agonists: analysis by nonlinear regression and application to N-methyl-D-aspartate receptors.
MedLine Citation:
PMID:  7902027     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The activation of a receptor by two agonists is described by a mathematical model based on the assumption that the response of the receptor is a linear function of its occupancy. The model has six parameters: the basal response, three efficacies corresponding to two binary and one ternary complexes, the affinities of the two agonists, and a parameter describing mutual changes in the affinity of the agonists. A method is described to determine the parameters of the model by two successive fittings to the logistic sigmoidal function using nonlinear regression. This method was applied to study the activation of N-methyl-D-aspartate receptors by glutamate and glycine, measured with [3H]-dizocilpine binding under nonequilibrium conditions. Experimental data fitted the model well, and consistent parameter values were obtained in three independent experiments. The efficacies with one agonist (glutamate or glycine) were very low compared with the efficacy with the two agonists combined, indicating that both glutamate and glycine are required for the activation of N-methyl-D-aspartate receptors. Glutamate and glycine also mutually increased their affinities for the receptor. This method may be useful for characterizing partial agonists, antagonists, and inverse agonists of receptors with multiple modulatory sites.
Authors:
J C Marvizón; M Baudry
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Analytical biochemistry     Volume:  213     ISSN:  0003-2697     ISO Abbreviation:  Anal. Biochem.     Publication Date:  1993 Aug 
Date Detail:
Created Date:  1993-12-03     Completed Date:  1993-12-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370535     Medline TA:  Anal Biochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3-11     Citation Subset:  IM    
Affiliation:
Neurobiology Program, University of Southern California, Los Angeles 90089-2520.
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MeSH Terms
Descriptor/Qualifier:
Animals
Binding Sites
Data Interpretation, Statistical
Dizocilpine Maleate / metabolism
Drug Interactions
Glutamates / pharmacology*
Glutamic Acid
Glycine / pharmacology*
Kinetics
Male
Mathematical Computing
Models, Biological
Prosencephalon / drug effects,  metabolism,  ultrastructure
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate / drug effects,  metabolism,  physiology*
Regression Analysis
Tritium
Chemical
Reg. No./Substance:
0/Glutamates; 0/Receptors, N-Methyl-D-Aspartate; 10028-17-8/Tritium; 56-40-6/Glycine; 56-86-0/Glutamic Acid; 77086-22-7/Dizocilpine Maleate

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


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