Nicotinic acetylcholine receptors: Conventional and unconventional ligands and signaling.
Nicotinic acetylcholine receptors: Conventional and unconventional ligands and signaling.
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烟碱乙酰胆碱受体：常规和非常规配体和信号传导。
DOI：
10.1016/j.neuropharm.2020.108021
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发表时间：
2020-05-15
影响因子：
4.7
通讯作者：
Lindstrom JM
中科院分区：
文献类型：
--
作者：
Papke RL;Lindstrom JM
外周神经系统突触后nachr对神经肌肉和自主神经传递至关重要。大脑突触前和突触周围的nachr调节神经传递，并负责尼古丁的成瘾效应。淋巴细胞和非突触位置的nachr亚型可能调节炎症和其他细胞功能。所有作为配体门控离子通道的achr都是由5个同源亚基组成一个中心阳离子通道，其开放由细胞外亚基界面上的ACh结合调节。nAChR亚型亚基组成可以从α7同聚体到α4β2α6β2β3异聚体。不同亚型对乙酰胆碱和其他激动剂如尼古丁的亲和力不同，它们的通道打开和脱敏的效率也不同。亚型对拮抗剂和正、负变构调节剂的亲和力也不同。一些激动剂对通道打开是“沉默的”，achr可能能够通过释放独立于通道打开的g蛋白来传递代谢途径的信号。电生理学研究可以解决单通道打开和分子遗传学方法，可以表征配体结合位点的结构，阳离子通道，它们之间的联系，以及AChR亚基的组织及其对功能的贡献。晶体学和低温电子显微镜技术为achr的结构和功能提供了越来越多的见解。然而，关于AChR的结构和功能，一些AChR亚型在体内的功能作用，以及针对AChR治疗成瘾、疼痛、炎症和其他医学上重要问题的更好的药理学工具的发展，还有很多有待了解的地方。
Postsynaptic nAChRs in the peripheral nervous system are critical for neuromuscular and autonomic neurotransmission. Pre- and peri-synaptic nAChRs in the brain modulate neurotransmission and are responsible for the addictive effects of nicotine. Subtypes of nAChRs in lymphocytes and non-synaptic locations may modulate inflammation and other cellular functions. All AChRs that function as ligand-gated ion channels are formed from five homologous subunits organized to form a central cation channel whose opening is regulated by ACh bound at extracellular subunit interfaces. nAChR subtype subunit composition can range from α7 homomers to α4β2α6β2β3 heteromers. Subtypes differ in affinities for ACh and other agonists like nicotine and in efficiencies with which their channels are opened and desensitized. Subtypes also differ in affinities for antagonists and for positive and negative allosteric modulators. Some agonists are “silent” with respect to channel opening, and AChRs may be able to signal metabotropic pathways by releasing G-proteins independent of channel opening. Electrophysiological studies that can resolve single-channel openings and molecular genetic approaches have allowed characterization of the structures of ligand binding sites, the cation channel, and the linkages between them, as well as the organization of AChR subunits and their contributions to function. Crystallography and cryo-electron-microscopy are providing increasing insights into the structures and functions of AChRs. However, much remains to be learned about both AChR structure and function, the in vivo functional roles of some AChR subtypes, and the development of better pharmacological tools directed at AChRs to treat addiction, pain, inflammation, and other medically important issues.
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DOI：
10.1073/pnas.1315775110
发表时间：
2013-12-17
影响因子：
11.1
作者：
Andersen, Natalia;Corradi, Jeremias;Bouzat, Cecilia
通讯作者：
Bouzat, Cecilia
影响因子：
7.3
作者：
Briggs, Clark A.;Gronlien, Jens Halvard;Gopalakrishnan, Murali
通讯作者：
Gopalakrishnan, Murali
影响因子：
4.7
作者：
Azam L;McIntosh JM
通讯作者：
McIntosh JM
DOI：
10.1073/pnas.84.21.7763
发表时间：
1987-11-01
影响因子：
11.1
作者：
BOULTER, J;CONNOLLY, J;PATRICK, J
通讯作者：
PATRICK, J
影响因子：
2.5
作者：
Buhler, AV;Dunwiddie, TV
通讯作者：
Dunwiddie, TV