Ethanol stimulates gamma-aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosomes.
The effects of ethanol on Cl- uptake were studied using a cell-free subcellular preparation from brain that contains a gamma-aminobutyric acid (GABA)/barbiturate receptor-sensitive Cl- transport system. In isolated vesicles prepared from rat cerebral cortex, ethanol, at concentrations that are present during acute intoxication (20-50 mM), stimulated 36Cl- uptake in a concentration-dependent and biphasic manner. The ethanol-stimulated uptake of 36Cl- was markedly inhibited by the GABA antagonists picrotoxin and bicuculline but not by a variety of other neurotransmitter receptor antagonists. The effects of ethanol in stimulating 36Cl- uptake in isolated brain vesicles were qualitatively and quantitatively similar to that of pentobarbital. Ethanol also markedly potentiated both muscimol- and pentobarbital-stimulated 36Cl- uptake at concentrations below those that directly stimulate 36Cl- uptake. Under our incubation conditions, ethanol did not release GABA, suggesting that it interacts with the postsynaptic GABA/barbiturate receptor complex. The ability of ethanol to stimulate GABA/barbiturate receptor-mediated Cl- transport may explain many of its pharmacological properties and provides a mechanism for the common psychopharmacological actions of ethanol, barbiturates, and benzodiazepines.
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002474:Cell-Free System; D002712:Chlorides / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D013574:Synaptosomes / Q000378:metabolism
D001640:Bicuculline; D002712:Chlorides; D000431:Ethanol; D007473:Ion Channels; D009118:Muscimol; D010424:Pentobarbital; D010852:Picrotoxin; D011963:Receptors, GABA-A