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Thermodynamics of Agonist and Antagonist Interaction with the Strychnine‐Sensitive Glycine Receptor
Author(s) -
RuizGómez Ana,
GarcíaCalvo Margarita,
Vázquez Jesús,
Marvizón Juan Carlos G.,
Valdivieso Fernando,
Mayor Federico
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb07256.x
Subject(s) - strychnine , glycine receptor , allosteric regulation , chemistry , glycine , receptor , agonist , binding site , bicuculline , antagonist , biophysics , stereochemistry , biochemistry , amino acid , biology
Abstract: The thermodynamic parameters associated with the interactions of agonists and antagonists with glycine receptors in rat spinal cord membranes were determined. The binding of the antagonist [ 3 H]strychnine and the inhibition of strychnine binding by 11 different glycinergic ligands were examined at temperatures between 0.5 and 37°C The density of receptors was not affected by the temperature at which the incubation was performed, but the ability of glycine receptor agonists and antagonists to compete with [ 3 H]strychnine binding varied markedly. The affinity of the receptor for the antagonists strychnine, 2‐aminostrychnine, RU‐5135,5,6,7,8‐tetrahydro‐4 H ‐Msoxazolo[5,4‐ c ]azepin‐3‐ol, and the ligands bicuculline, norharmane, and PK‐8165 decreased at higher temperatures. The binding of these ligands was enthalpydriven. In contrast, the affinity of the agonists glycine, β‐alanine, and taurine and of the antihelmintic ivermectin increased at higher temperatures, and their binding was characterized by substantial increases in entropy. In addition, temperature affected the allosteric interaction between the glycine and strychnine sites of the receptor, as indicated by changes in the Hill number of the competition curves for glycine. Our results clearly indicate that the binding of agonists and antagonists to the glycine receptor is differentially affected by temperature, probably as a consequence of the different changes induced in the receptor conformation.