Modulation of the Benzodiazepine/γ‐Aminobutyric Acid Receptor Chloride Channel Complex by Inhalation Anesthetics

Eric J. Moody, P. D. Suzdak, S. M. Paul, P. Skolnick

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Abstract: Inhalation anesthetics, such as diethyl ether, halo‐thane, and enflurane, increase 36C1 uptake into rat cerebral cortical synaptoneurosomes in a concentration‐dependent, picrotoxin‐sensitive fashion. At concentrations consistent with those that stimulate 36C1 uptake, inhalation anesthetics also inhibit the binding of t‐[35S]butylbicyclophosphoro‐thionate ([35S]TBPS) to well‐washed cortical membranes. Scatchard analysis of [35S]TBPS binding indicates that these agents reduce the apparent affinity of this radioligand and have little effect on the Bmax. The ability of inhalation anesthetics to directly stimulate 36C1 uptake and inhibit [35S]TBPS binding is a property shared by nonvolatile anesthetics. Nonetheless, there are differences between nonvolatile agents (such as barbiturates and alcohols) and in halation anesthetics, because the former compounds augment muscimol (a GABAmimetic) stimulated 36C1 uptake, whereas the latter group (such as ether and enflurane) inhibit this effect. These findings demonstrate that therapeutically relevant concentrations of inhalation anesthetics perturb the benzodiazepine/γ‐aminobutyric acid receptor chloride channel complex, and suggest this oligomeric protein may be a common mediator of some aspects of anesthetic action.

Original languageEnglish
Pages (from-to)1386-1393
Number of pages8
JournalJournal of Neurochemistry
Volume51
Issue number5
DOIs
StatePublished - Nov 1988

Keywords

  • Anesthetics
  • Chloride uptake
  • Enflurane
  • Ether
  • t‐Butylbicyclophosphorothionate
  • γ‐Aminobutyric acid

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