From kinetics and thermodynamics of GABAA receptor binding to ionophore function.

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The time- and temperature-dependencies of binding are overviewed for the benzodiazepine, GABA and convulsant binding sites of the GABAA receptor-ionophore complex. Kinetic separation of the dissociation phases of a beta-carboline inverse agonist demonstrated the heterogeneity of its binding sites. The kinetics and thermodynamics of benzodiazepine binding alone do not correlate with ionophore function. The majority of the data suggest that agonist- and antagonist-preferring conformations exist for GABAA receptors. The high affinity binding of GABAA antagonists (SR 95531 and bicuculline) corresponds to the (super) low affinity binding of GABA. The correlation between the thermodynamic parameters of binding and efficacies common for GABAA and glycine receptor agonists and antagonists supports the functional similarities of these anionophore complexes. Binding kinetics of the bicyclic cage convulsants show several correlations with ionophore function because the convulsant sites are most intimately coupled to the ion channels. Kinetic interactions of the convulsant sites with the binding sites of benzodiazepines, GABA and central depressants have revealed several pharmacologically relevant allosteric GABAergic modulatory effects. Arrhenius analysis, Hammond's postulate and transition state theory were applied for the dissociation of convulsants. A kinetic model of interconvertible multiaffinity states of the convulsant sites shows correlations with the functional states of the GABAA ionophore.

Original languageEnglish
Pages (from-to)361-370
Number of pages10
JournalNeurochemistry International
Volume29
Issue number4
Publication statusPublished - Oct 1996

Fingerprint

Convulsants
Ionophores
GABA-A Receptors
Thermodynamics
Benzodiazepines
gamma-Aminobutyric Acid
GABA-A Receptor Antagonists
norharman
Binding Sites
GABA Agents
GABA-A Receptor Agonists
Glycine Receptors
Bicuculline
Ion Channels
Temperature

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

From kinetics and thermodynamics of GABAA receptor binding to ionophore function. / Maksay, G.

In: Neurochemistry International, Vol. 29, No. 4, 10.1996, p. 361-370.

Research output: Contribution to journalArticle

@article{1793f97cdb424f72ab3d45b3f64ed2d9,
title = "From kinetics and thermodynamics of GABAA receptor binding to ionophore function.",
abstract = "The time- and temperature-dependencies of binding are overviewed for the benzodiazepine, GABA and convulsant binding sites of the GABAA receptor-ionophore complex. Kinetic separation of the dissociation phases of a beta-carboline inverse agonist demonstrated the heterogeneity of its binding sites. The kinetics and thermodynamics of benzodiazepine binding alone do not correlate with ionophore function. The majority of the data suggest that agonist- and antagonist-preferring conformations exist for GABAA receptors. The high affinity binding of GABAA antagonists (SR 95531 and bicuculline) corresponds to the (super) low affinity binding of GABA. The correlation between the thermodynamic parameters of binding and efficacies common for GABAA and glycine receptor agonists and antagonists supports the functional similarities of these anionophore complexes. Binding kinetics of the bicyclic cage convulsants show several correlations with ionophore function because the convulsant sites are most intimately coupled to the ion channels. Kinetic interactions of the convulsant sites with the binding sites of benzodiazepines, GABA and central depressants have revealed several pharmacologically relevant allosteric GABAergic modulatory effects. Arrhenius analysis, Hammond's postulate and transition state theory were applied for the dissociation of convulsants. A kinetic model of interconvertible multiaffinity states of the convulsant sites shows correlations with the functional states of the GABAA ionophore.",
author = "G. Maksay",
year = "1996",
month = "10",
language = "English",
volume = "29",
pages = "361--370",
journal = "Neurochemistry International",
issn = "0197-0186",
publisher = "Elsevier Limited",
number = "4",

}

TY - JOUR

T1 - From kinetics and thermodynamics of GABAA receptor binding to ionophore function.

AU - Maksay, G.

PY - 1996/10

Y1 - 1996/10

N2 - The time- and temperature-dependencies of binding are overviewed for the benzodiazepine, GABA and convulsant binding sites of the GABAA receptor-ionophore complex. Kinetic separation of the dissociation phases of a beta-carboline inverse agonist demonstrated the heterogeneity of its binding sites. The kinetics and thermodynamics of benzodiazepine binding alone do not correlate with ionophore function. The majority of the data suggest that agonist- and antagonist-preferring conformations exist for GABAA receptors. The high affinity binding of GABAA antagonists (SR 95531 and bicuculline) corresponds to the (super) low affinity binding of GABA. The correlation between the thermodynamic parameters of binding and efficacies common for GABAA and glycine receptor agonists and antagonists supports the functional similarities of these anionophore complexes. Binding kinetics of the bicyclic cage convulsants show several correlations with ionophore function because the convulsant sites are most intimately coupled to the ion channels. Kinetic interactions of the convulsant sites with the binding sites of benzodiazepines, GABA and central depressants have revealed several pharmacologically relevant allosteric GABAergic modulatory effects. Arrhenius analysis, Hammond's postulate and transition state theory were applied for the dissociation of convulsants. A kinetic model of interconvertible multiaffinity states of the convulsant sites shows correlations with the functional states of the GABAA ionophore.

AB - The time- and temperature-dependencies of binding are overviewed for the benzodiazepine, GABA and convulsant binding sites of the GABAA receptor-ionophore complex. Kinetic separation of the dissociation phases of a beta-carboline inverse agonist demonstrated the heterogeneity of its binding sites. The kinetics and thermodynamics of benzodiazepine binding alone do not correlate with ionophore function. The majority of the data suggest that agonist- and antagonist-preferring conformations exist for GABAA receptors. The high affinity binding of GABAA antagonists (SR 95531 and bicuculline) corresponds to the (super) low affinity binding of GABA. The correlation between the thermodynamic parameters of binding and efficacies common for GABAA and glycine receptor agonists and antagonists supports the functional similarities of these anionophore complexes. Binding kinetics of the bicyclic cage convulsants show several correlations with ionophore function because the convulsant sites are most intimately coupled to the ion channels. Kinetic interactions of the convulsant sites with the binding sites of benzodiazepines, GABA and central depressants have revealed several pharmacologically relevant allosteric GABAergic modulatory effects. Arrhenius analysis, Hammond's postulate and transition state theory were applied for the dissociation of convulsants. A kinetic model of interconvertible multiaffinity states of the convulsant sites shows correlations with the functional states of the GABAA ionophore.

UR - http://www.scopus.com/inward/record.url?scp=0029658482&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029658482&partnerID=8YFLogxK

M3 - Article

C2 - 8939444

AN - SCOPUS:0029658482

VL - 29

SP - 361

EP - 370

JO - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

IS - 4

ER -