Article date: 1991/3/1
PubMed ID: 1647705
Journal name: Alcoholism, clinical and experimental research (ISSN: 0145-6008)
Low concentrations of ethanol (10-30 mM) in the presence of a GABAB receptor agonist, baclofen, promoted 36Cl- uptake into membrane vesicles (microsacs) prepared from mouse cortex. Neither ethanol nor baclofen alone altered chloride influx. The GABAB antagonists, phaclofen and 2-hydroxy-saclofen, completely blocked the increase in chloride flux produced by ethanol in the presence of either baclofen or GABA. Ethanol increased the chloride conductance produced by the GABAA agonists muscimol, isoguvacine, imidazolacetic acid and amino-propane sulfonic acid and this action of ethanol was blocked by phaclofen. The specific GABAA antagonist, bicuculline, blocked ethanol-induced increase in chloride flux in the presence of either baclofen or GABA. GABA-activated chloride channels were also studied in Xenopus oocytes expressing mouse brain mRNA. In this preparation, GABA action was enhanced by ethanol, pentobarbital, and diazepam, and 2-hydroxy-saclofen partially antagonized the action of ethanol without altering the effects of pentobarbital or diazepam. These results suggest that ethanol enhancement of GABAA receptor-chloride channel function also requires activation of GABAB receptors.
Author List: Allan A M, Burnett D, Harris R A
Publication Types: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Chloride Channels; Chlorides; Membrane Proteins; Receptors, GABA-A; phaclofen; Ethanol; Baclofen; Bicuculline;
Mesh terms: Alcohol Drinking/physiopathology; Animals; Baclofen/analogs & derivatives; Bicuculline/pharmacology; Cerebral Cortex/drug effects; Chloride Channels; Chlorides/metabolism; Dose-Response Relationship, Drug; Drug Synergism; Ethanol/pharmacology; Male; Membrane Proteins/drug effects; Mice; Mice, Inbred ICR; Receptors, GABA-A/classification;