Cardoso R A, Brozowski S J, Chavez-Noriega L E, Harpold M, Valenzuela C F, Harris R A
Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
J Pharmacol Exp Ther. 1999 May;289(2):774-80.
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 in Xenopus oocytes. Ethanol (75 mM) potentiated ACh-induced currents in alpha2beta4, alpha4beta4, alpha2beta2, and alpha4beta2 receptors. This effect was due to an increase in Emax, without a change in the EC50 or Hill coefficient. hnAChR alpha2beta4 did not develop tolerance to repeated applications of ethanol or continuous exposure (10 min). The alpha3beta2 and alpha3beta4 combinations were insensitive to ethanol. Low concentrations of ethanol (25 and 50 mM) significantly inhibited homomeric alpha7 receptor 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.
在人类中，酒精和烟草的使用高度相关，并且动物模型研究表明酒精与神经元烟碱型乙酰胆碱受体（nAChRs）存在相互作用。本研究的目的是表征急性乙醇处理对非洲爪蟾卵母细胞中表达的不同组合的人nAChR（hnAChR）亚基的影响。乙醇（75 mM）增强了α2β4、α4β4、α2β2和α4β2受体中乙酰胆碱诱导的电流。这种效应是由于Emax增加，而EC50或希尔系数没有变化。hnAChRα2β4对乙醇的重复应用或持续暴露（10分钟）没有产生耐受性。α3β2和α3β4组合对乙醇不敏感。低浓度的乙醇（25和50 mM）显著抑制同源α7受体功能，但这些受体对乙醇表现出高度可变的反应。这些结果表明乙醇对hnAChRs的影响取决于受体亚基组成。鉴于最近有证据表明nAChRs介导和调节中枢神经系统中的突触传递，我们推测急性中毒可能涉及乙醇诱导的这些受体功能改变。
