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

Journal Article · Tue Apr 24 00:00:00 EDT 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00468a028· OSTI ID:6277389

Lamdani-Itkin, H; Kloog, Y; Sokolovsky, M ^[1]

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1. Tel Aviv Univ. (Israel)

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.

• OSTI ID: 6277389
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:16; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
AMINO ACIDS
ANIMALS
ASPARTIC ACID
AZINES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARBOXYLIC ACID ESTERS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CEREBRUM
DOSE-RESPONSE RELATIONSHIPS
ESTERS
GLUTAMIC ACID
GLYCINE
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PIPERIDINES
PROTEINS
PYRIDINES
RADIORECEPTOR ASSAY
RATS
REACTION KINETICS
RECEPTORS
RODENTS
TEMPERATURE DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES