Ethanol and the gamma-aminobutyric acid-benzodiazepine receptor complex.
Ethanol appears to enhance gamma-aminobutyric acid (GABA)-mediated synaptic transmission. Using radioligand binding techniques, we investigated the possibility that the GABA-benzodiazepine receptor complex is the site responsible for this effect. Ethanol at concentrations up to 100 mM failed to alter binding of [3H]flunitrazepam (FNZ), [3H]Ro 15-1788, or [3H]methyl-beta-carboline-3-carboxylate (MBCC) to benzodiazepine receptors, or of [3H]muscimol to GABA receptors in rat brain membranes. Scatchard analyses of the binding of these radioligands at 4 degrees C and 37 degrees C revealed no significant effects of 100 mM ethanol on receptor affinity or number. A variety of drugs as well as chloride ion increased binding of [3H]FNZ and/or [3H]muscimol, but these influences were not modified by ethanol. These findings indicate that ethanol probably potentiates GABAergic neurotransmission at a signal transduction site beyond the GABA-benzodiazepine receptor complex.
D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002243:Carbolines / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005442:Flumazenil; D005445:Flunitrazepam / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000378:metabolism; D009118:Muscimol / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A; D013696:Temperature; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001570:Benzodiazepinones; D002243:Carbolines; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; C026072:1-methyl-beta-carboline-3-carboxylic acid; D009118:Muscimol; D000431:Ethanol; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam