Ethanol potentiation of GABAergic transmission in cultured spinal cord neurons involves gamma-aminobutyric acidA-gated chloride channels

Journal Article · Mon Aug 01 04:00:00 EDT 1988 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:7036815

Mehta, A K; Ticku, M K

The interaction of ethanol with gamma-aminobutyric acid (GABA)-mediated 36-Cl-influx and its modulation by various drugs was investigated in C57 mice spinal cord cultured neurons. Ethanol (5-100 mM) potentiated the effect of GABA on /sup 36/Cl-influx; whereas at concentrations greater than or equal to 50 mM ethanol activated Cl- channels directly. The effect of ethanol was specific for GABAA receptor-gated Cl- channels, as ethanol did not potentiate glycine-induced /sup 36/Cl-influx in the same neurons. Both the enhancing and direct effects of ethanol on /sup 36/Cl-influx were blocked by GABA antagonists like bicuculline, picrotoxinin and inverse agonists of the benzodiazepine site like the imidazodiazepine R015-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo (1,5 alpha), (1,4)benzodiazepine-3-carboxylate) and N-methyl-beta-carboline-3-carboxamide (FG-7142). Ethanol potentiating effect of GABA-induced /sup 36/Cl-influx was also reversed by methyl-6,7-dimethyl-4-ethyl-beta-carboline-3-carboxylate. The effects of the inverse agonists were blocked by the benzodiazepine receptor antagonist R015-1788. Both R015-4513 and FG-7142 reversed direct and GABA potentiating effects of ethanol effect at concentrations lower than those that exhibit inverse agonistic activity in the /sup 36/Cl-influx assay in cultured neurons. These results suggest that ethanol facilitation of GABAAergic transmission involves GABA receptor-gated Cl- channels and that this interaction may be responsible for some of the pharmacological effects of ethanol.

• Research Organization: Univ. of Texas Health Science Center, San Antonio (USA)
• OSTI ID: 7036815
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 246:2; ISSN JPETA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
AMINO ACIDS
AMINOBUTYRIC ACID
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZIDES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOSYNTHESIS
CARBOXYLIC ACIDS
CELL CULTURES
CENTRAL NERVOUS SYSTEM
CHLORINE
CHLORINE 36
CHLORINE ISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
ETHANOL
HALOGENS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
MICE
NERVE CELLS
NERVOUS SYSTEM
NEUROREGULATORS
NITROGEN COMPOUNDS
NONMETALS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
RECEPTORS
RODENTS
SOMATIC CELLS
SPINAL CORD
SYNTHESIS
TRACER TECHNIQUES
VERTEBRATES
YEARS LIVING RADIOISOTOPES