| Receptor activation by two agonists: analysis by nonlinear regression and application to N-methyl-D-aspartate receptors. | |
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MedLine Citation:
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PMID: 7902027 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J C Marvizón; M Baudry |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Analytical biochemistry Volume: 213 ISSN: 0003-2697 ISO Abbreviation: Anal. Biochem. Publication Date: 1993 Aug |
Date Detail:
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Created Date: 1993-12-03 Completed Date: 1993-12-03 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370535 Medline TA: Anal Biochem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 3-11 Citation Subset: IM |
Affiliation:
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Neurobiology Program, University of Southern California, Los Angeles 90089-2520. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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