S2A-3 The Alpha6*-nAChR is A Highly Sensitive Target for Low Dose Alcohol  

作　　者：WU Jie 

机构地区：[1]Division of Neurology,Barrow Neurological Institute,St.Joseph’s Hospital and Medical Center,Phoenix AZ 85013,USA

出　　处：《神经药理学报》2018年第4期36-37,共2页Acta Neuropharmacologica

摘　　要：Alcohol use disorder(AUD)is a serious public health problem that affects approximately 17 million Americans and results in tremendous social,legal and medical costs to the society.Unlike other addictive drugs(e.g.,morphine,cocaine or nicotine)that have specific molecular targets,ethanol(EtOH)has no specific target.In most previous studies,EtOH concentrations used for investigation were too high(e.g.,>50 mmol·L-1)compared to the EtOH concentrations in human brain after alcohol drinking,and the high dose EtOH may produce nonspecific modulations of a variety of receptors,ion channels,intracellular signaling cascades,and gene expression in the brain.Therefore,it is important to understand low dose(e.g.,<10 mmol·L-1)EtOH effects in the brain.Unfortunately,the molecular and cellular targets that mediate the sensitivity to low dose EtOH remain to be defined.nAChRs containingα6 subunits(α6*-nAChRs)shows a highly restricted distribution in midbrain dopaminergic neurons that are associated with drug dependence and addiction.Here,we report that low dose EtOH(0.1~5 mmol·L-1)significantly potentiatesα6*-nAChR function using patch-clamp whole-cell recordings.Since EtOH modulatesα6*-nAChR-mediated function depending on both EtOH and nicotine concentrations,representing a positive allosteric modulation.In conclusion,our results demonstrate a functionalα6*-nAChR transfected in human SH-EP1 cells that can be used as an excellent cell model to investigateα6*-nAChR function and pharmacology.Under patch-clamp recording condition,low dose EtOH modulatesα6*-nAChR function as a positive allosteric modulator.Through this mechanism,brainα6*-nAChRs may play a critical role in mediating low dose alcohol’effects on alcohol reward and dependence.

关 键 词：ETOH MEDIATE the sensitivity 

分 类 号：R73[医药卫生—肿瘤]