Alcohols stimulate gamma-aminobutyric acid receptor-mediated chloride uptake in brain vesicles: correlation with intoxication potency.
A series of short-chain alcohols, including ethanol, were examined for their abilities to stimulate gamma-aminobutyric acid (GABA) receptor-mediated chloride uptake into isolated brain vesicles. All of the alcohols tested stimulated 36 chloride uptake, at concentrations that occur during acute intoxication, and their potencies in stimulating GABA receptor-mediated chloride uptake were highly correlated with both their intoxication potencies in rats (r = 0.96; P less than 0.0001) and their membrane/buffer partition coefficients (r = 0.91; P less than 0.0005). Thus, the activity of alcohols at the GABA receptor-coupled chloride ion channel appears to be related to their ability to enter hydrophobic regions of the neuronal membrane. These data suggest that the anxiolytic, sedative/hypnotic and intoxicating properties of ethanol may, in part, be mediated via an action at central GABA receptors.
Suzdak
P D
PD
Section on Molecular Pharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Schwartz
R D
RD
Skolnick
P
P
Paul
S M
SM
D000435:Alcoholic Intoxication / Q000139:chemically induced; D000438:Alcohols / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D009994:Osmolar Concentration; D011963:Receptors, GABA-A / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism*
D000438:Alcohols; D002712:Chlorides; D011963:Receptors, GABA-A