Differential modulation of rat neuronal nicotinic receptor subtypes by acute application of ethanol
Differential modulation of rat neuronal nicotinic receptor subtypes by acute application of ethanol
复制标题
DOI：
10.1038/sj.bjp.0701568
复制
发表时间：
1997-12-01
影响因子：
7.3
通讯作者：
Connolly, JG
中科院分区：
文献类型：
--
作者：
Covernton, PJO;Connolly, JG
1用电压钳技术研究了急性乙醇暴露对非洲爪哇卵母细胞表达的大鼠神经元烟碱受体激动剂反应的影响。2在某些细胞中，低浓度乙醇(1-30 mM)可显著增强或抑制α3β4亚单位的激动剂诱导的电流反应(为对照反应的25%~237%)。3低乙醇浓度对α3β4亚型的影响表现出对乙醇重复暴露的耐受性。4总的来说，α3β2、α4-1β2和α4-1β4亚单位组合对低浓度乙醇不敏感，但在高浓度乙醇时分别表现出高达178%、226%和154%的增强。在高浓度的乙醇作用下，可观察到控制激动剂反应的增强、抑制或无变化(范围为对照的88%至141%)。6我们得出结论，所有被测试的神经元烟碱受体亚单位组合都可以被高浓度的乙醇以一种快速可逆的方式调节。这种调节可能是乙醇的一些行为效应的基础。α3β4亚单位组合可能对低浓度乙醇的调节特别敏感。尼古丁受体的这种非凡的敏感性和可塑性可能有助于尼古丁和酒精成瘾的相互加强过程。
1 We have studied the effects of acute ethanol (EtOH) exposure on the agonist responses of rat neuronal nicotinic receptors expressed in Xenopus oocytes by means of voltage clamp techniques.2 In some cells, agonist-induced current responses with the alpha 3 beta 4 subunit combination could be either significantly potentiated or inhibited (range 25% to 237% of control response) by low ethanol concentrations (1-30 mM). At high ethanol concentrations (100-300 mM) robust potentiations were observed (range 135% to 305% of control).3 The low EtOH concentration effects on the alpha 3 beta 4 subtype exhibited tolerance with repeated EtOH exposure.4 In general, the alpha 3 beta 2, alpha 4-1 beta 2 and alpha 4-1 beta 4 subunit combinations were less sensitive to low concentrations of ethanol, but respectively showed potentiations of up to 178%, 226% and 154% at high EtOH concentrations.5 The alpha 7 homomeric receptor was also relatively insensitive at low EtOH concentrations. At high EtOH concentrations, potentiations, inhibitions or no alteration of control agonist response were observed (range 88% to 141% of control).6 We conclude that all the neuronal nicotinic receptor subunit combinations tested here can be modulated by high concentrations of EtOH in a rapidly reversible manner. This modulation may underlie some of the behavioural effects of ethanol. The alpha 3 beta 4 subunit combination may be especially sensitive to modulation by low EtOH concentrations. This remarkable sensitivity and plasticity of nicotinic receptors may contribute to a process of mutual reinforcement in nicotine and alcohol addiction.