Thermodynamics of agonist and antagonist interaction with the strychnine-sensitive glycine receptor.

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 [3H]strychnine and the inhibition of strychnine binding by 11 different glycinergic ligands were examined at temperatures between 0.5 and 37 degrees 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 [3H]strychnine binding varied markedly. The affinity of the receptor for the antagonists strychnine, 2-aminostrychnine, RU-5135, 5,6,7,8-tetrahydro-4H-isoxazolo[5,4-c]azepin-3-ol, and the ligands bicuculline, norharmane, and PK-8165 decreased at higher temperatures. The binding of these ligands was enthalpy-driven. In contrast, the affinity of the agonists glycine, beta-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.

journal_name

J Neurochem

authors

Ruiz-Gómez A,García-Calvo M,Vázquez J,Marvizón JC,Valdivieso F,Mayor F Jr

doi

10.1111/j.1471-4159.1989.tb07256.x

subject

Has Abstract

pub_date

1989-06-01 00:00:00

pages

1775-80

issue

6

eissn

0022-3042

issn

1471-4159

journal_volume

52

pub_type

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