Effects of ethanol on recombinant human neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes

Alcohol and tobacco use is highly correlated in humans, and studies with an imal models suggest an interaction of alcohol with neuronal nicotinic acety lcholine receptors (nAChRs), The aim of the present study was to characteri ze the effect of acute ethanol treatment on different combinations of human nAChR (hnAChR) subunits expressed in Xenopus oocytes. Ethanol (75 mM) pote ntiated ACh-induced currents in alpha(2)beta(4), alpha(4)beta(4), alpha(2)b eta(2), and alpha(4)beta(2) receptors. This effect was due to an increase i n E-max, without a change in the EC50 or Hill coefficient. hnAChR alpha(2)b eta(4) did not develop tolerance to repeated applications of ethanol or con tinuous exposure (10 min). The alpha(3)beta(2) and alpha(3)beta(4) combinat ions were insensitive to ethanol. Low concentrations of ethanol (25 and 50 mM) significantly inhibited homomeric alpha(7) receptor function, but these receptors showed highly variable responses to ethanol. These results indic ate that ethanol effects on hnAChRs depend on the receptor subunit composit ion. In light of recent evidence indicating that nAChRs mediate and modulat e synaptic transmission in the central nervous system, we postulate that ac ute intoxication might involve ethanol-induced alterations in the function of these receptors.