Abstract

Alcohol and tobacco use is highly correlated in humans, and studies with animal models suggest an interaction of alcohol with neuronal nicotinic acetylcholine receptors (nAChRs). The aim of the present study was to characterize the effect of acute ethanol treatment on different combinations of human nAChR (hnAChR) subunits expressed inXenopus oocytes. Ethanol (75 mM) potentiated ACh-induced currents in α₂β₄, α₄β₄, α₂β₂, and α₄β₂ receptors. This effect was due to an increase in E _max, without a change in the EC₅₀ or Hill coefficient. hnAChR α₂β₄ did not develop tolerance to repeated applications of ethanol or continuous exposure (10 min). The α₃β₂ and α₃β₄combinations were insensitive to ethanol. Low concentrations of ethanol (25 and 50 mM) significantly inhibited homomeric α₇receptor function, but these receptors showed highly variable responses to ethanol. These results indicate that ethanol effects on hnAChRs depend on the receptor subunit composition. In light of recent evidence indicating that nAChRs mediate and modulate synaptic transmission in the central nervous system, we postulate that acute intoxication might involve ethanol-induced alterations in the function of these receptors.