McGehee D S, Heath M J, Gelber S, Devay P, Role L W
Department of Cell Biology and Anatomy, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Science. 1995 Sep 22;269(5231):1692-6. doi: 10.1126/science.7569895.
The behavioral and cognitive effects of nicotine suggest that nicotinic acetylcholine receptors (nAChRs) participate in central nervous system (CNS) function. Although nAChR subunit messenger RNA (mRNA) and nicotine binding sites are common in the brain, there is little evidence for synapses mediated by nAChRs in the CNS. To test whether, CNS nAChRs might modify rather than mediate transmission, the regulation of excitatory synaptic transmission by these receptors was examined. Nanomolar concentrations of nicotine enhanced both glutamatergic and cholinergic synaptic transmission by activation of presynaptic nAChRs that increased presynaptic [Ca2]i. Pharmacological and subunit deletion experiments reveal that these presynaptic nAChRs include the alpha 7 subunit. These findings reveal that CNS nAChRs enhance fast excitatory transmission, providing a likely mechanism for the complex behavioral effects of nicotine.
尼古丁的行为和认知效应表明，烟碱型乙酰胆碱受体（nAChRs）参与中枢神经系统（CNS）功能。尽管nAChR亚基信使核糖核酸（mRNA）和尼古丁结合位点在大脑中很常见，但几乎没有证据表明CNS中存在由nAChRs介导的突触。为了测试CNS中的nAChRs是否可能改变而非介导传递，研究了这些受体对兴奋性突触传递的调节作用。纳摩尔浓度的尼古丁通过激活增加突触前[Ca2]i的突触前nAChRs，增强了谷氨酸能和胆碱能突触传递。药理学和亚基缺失实验表明，这些突触前nAChRs包括α7亚基。这些发现揭示了CNS中的nAChRs增强快速兴奋性传递，为尼古丁复杂的行为效应提供了一种可能的机制。
