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Title: Modulation of glutamate-induced uncompetitive blocker binding to the NMDA receptor by temperature and by glycine

Abstract

The effect of temperature on the binding of ({sup 3}H)-N-(1-(2-thienyl)cyclohexyl)piperidine (({sup 3}H)TCP) to the ion channel of the N-methyl-D-aspartate (NMDA) receptors was studied in washed rat brain-cortex membranes. Raising the temperature from 5 to 33{degree}C resulted in a significant increase in the association rates of ({sup 3}H)TCP binding measured in the presence of 1 {mu}M glutamate and 1 {mu}M glycine, but was less effective in the absence of the added agonists. No such effects of temperature on the dissociation rates of ({sup 3}H)TCP-receptor complexes were observed. In the absence of agonists, neither the association nor the dissociation binding components varied with temperature, suggesting a diffusion-controlled limitation of access of the ligand to its site within the nonactivated NMDA receptor. No evidence was found for a temperature-dependent change in the density of ({sup 3}H)TCP binding sites or for heterogeneity of ({sup 3}H)TCP binding sites associated with the NMDA receptor, even though when approaching equilibrium the binding kinetics in the presence of glutamate and glycine deviated from an ordinary bimolecular reaction scheme. The data were fitted instead to a two-exponent binding function, comprising the sum of a fast and a slow binding component. The results suggest homogeneity of ({sup 3}H)TCP-binding domains withinmore » the NMDA receptor channel but variability of total channel opening time. The observed effects of glutamate and of glycine on the kinetic components are consistent with this suggestion.« less

Authors:
; ;  [1]
  1. (Tel Aviv Univ. (Israel))
Publication Date:
OSTI Identifier:
6277389
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemistry; (USA); Journal Volume: 29:16
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; AMINO ACIDS; RECEPTORS; PIPERIDINES; RADIORECEPTOR ASSAY; ASPARTIC ACID; BIOCHEMICAL REACTION KINETICS; CARBOXYLIC ACID ESTERS; CELL MEMBRANES; CEREBRUM; DOSE-RESPONSE RELATIONSHIPS; GLUTAMIC ACID; GLYCINE; RATS; TEMPERATURE DEPENDENCE; TRITIUM COMPOUNDS; AMINES; ANIMALS; AZINES; BODY; BRAIN; CARBOXYLIC ACIDS; CELL CONSTITUENTS; CENTRAL NERVOUS SYSTEM; ESTERS; HETEROCYCLIC COMPOUNDS; HYDROGEN COMPOUNDS; ISOTOPE APPLICATIONS; KINETICS; MAMMALS; MEMBRANE PROTEINS; MEMBRANES; NERVOUS SYSTEM; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PROTEINS; PYRIDINES; REACTION KINETICS; RODENTS; TRACER TECHNIQUES; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Lamdani-Itkin, H., Kloog, Y., and Sokolovsky, M.. Modulation of glutamate-induced uncompetitive blocker binding to the NMDA receptor by temperature and by glycine. United States: N. p., 1990. Web. doi:10.1021/bi00468a028.
Lamdani-Itkin, H., Kloog, Y., & Sokolovsky, M.. Modulation of glutamate-induced uncompetitive blocker binding to the NMDA receptor by temperature and by glycine. United States. doi:10.1021/bi00468a028.
Lamdani-Itkin, H., Kloog, Y., and Sokolovsky, M.. Tue . "Modulation of glutamate-induced uncompetitive blocker binding to the NMDA receptor by temperature and by glycine". United States. doi:10.1021/bi00468a028.
@article{osti_6277389,
title = {Modulation of glutamate-induced uncompetitive blocker binding to the NMDA receptor by temperature and by glycine},
author = {Lamdani-Itkin, H. and Kloog, Y. and Sokolovsky, M.},
abstractNote = {The effect of temperature on the binding of ({sup 3}H)-N-(1-(2-thienyl)cyclohexyl)piperidine (({sup 3}H)TCP) to the ion channel of the N-methyl-D-aspartate (NMDA) receptors was studied in washed rat brain-cortex membranes. Raising the temperature from 5 to 33{degree}C resulted in a significant increase in the association rates of ({sup 3}H)TCP binding measured in the presence of 1 {mu}M glutamate and 1 {mu}M glycine, but was less effective in the absence of the added agonists. No such effects of temperature on the dissociation rates of ({sup 3}H)TCP-receptor complexes were observed. In the absence of agonists, neither the association nor the dissociation binding components varied with temperature, suggesting a diffusion-controlled limitation of access of the ligand to its site within the nonactivated NMDA receptor. No evidence was found for a temperature-dependent change in the density of ({sup 3}H)TCP binding sites or for heterogeneity of ({sup 3}H)TCP binding sites associated with the NMDA receptor, even though when approaching equilibrium the binding kinetics in the presence of glutamate and glycine deviated from an ordinary bimolecular reaction scheme. The data were fitted instead to a two-exponent binding function, comprising the sum of a fast and a slow binding component. The results suggest homogeneity of ({sup 3}H)TCP-binding domains within the NMDA receptor channel but variability of total channel opening time. The observed effects of glutamate and of glycine on the kinetic components are consistent with this suggestion.},
doi = {10.1021/bi00468a028},
journal = {Biochemistry; (USA)},
number = ,
volume = 29:16,
place = {United States},
year = {Tue Apr 24 00:00:00 EDT 1990},
month = {Tue Apr 24 00:00:00 EDT 1990}
}