Modulation of the benzodiazepine/gamma-aminobutyric acid receptor chloride channel complex by inhalation anesthetics.

Article date: 1988/11/1

PubMed ID: 2459308

Journal name: Journal of neurochemistry (ISSN: 0022-3042)


Inhalation anesthetics, such as diethyl ether, halothane, and enflurane, increase 36Cl- uptake into rat cerebral cortical synaptoneurosomes in a concentration-dependent, picrotoxin-sensitive fashion. At concentrations consistent with those that stimulate 36Cl- uptake, inhalation anesthetics also inhibit the binding of t-[35S]butylbicyclophosphorothionate ([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 36Cl- 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 inhalation anesthetics, because the former compounds augment muscimol (a GABAmimetic) stimulated 36Cl- 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/gamma-aminobutyric acid receptor chloride channel complex, and suggest this oligomeric protein may be a common mediator of some aspects of anesthetic action.

This document is available from: http://directlinks.cc/files/muscimol/2459308.pdf

Author List: Moody E J, Suzdak P D, Paul S M, Skolnick P

Publication Types: Comparative Study; Journal Article

Substances mentioned in the article: Anesthetics; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Chlorides; Ion Channels; Receptors, GABA-A; Ether; Muscimol; Methoxyflurane; tert-butylbicyclophosphorothionate; Enflurane; Pentobarbital; Halothane;

Mesh terms: Anesthesia, Inhalation; Anesthetics/pharmacology; Animals; Bridged Bicyclo Compounds/metabolism; Bridged Bicyclo Compounds, Heterocyclic; Cerebral Cortex/metabolism; Chlorides/metabolism; Enflurane/pharmacology; Ether/pharmacology; Halothane/pharmacology; Ion Channels/metabolism; Male; Methoxyflurane/pharmacology; Muscimol/pharmacology; Pentobarbital/pharmacology; Rats; Rats, Inbred Strains; Receptors, GABA-A/drug effects; Synaptosomes/metabolism;

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