Heterogeneity and complexity of native brain nicotinic receptors
Heterogeneity and complexity of native brain nicotinic receptors
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DOI：
10.1016/j.bcp.2007.05.023
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发表时间：
2007-10-15
影响因子：
5.8
通讯作者：
Zoli, Michele
中科院分区：
文献类型：
--
作者：
Gotti, Cecilia;Moretti, Milena;Zoli, Michele
神经元胆碱能烟碱受体（neuronalcholinergicnicotinicreceptor，nAChRs）是一类广泛分布于神经系统的具有特异性功能和药理学特性的阳离子通道。它们由一个大的多基因家族编码的同源亚基组成，它们的开放在生理上由乙酰胆碱神经递质或外源性配体（如尼古丁）控制。它们的生物物理和药理学特性取决于它们的亚基组成，因此，亚基组成对于理解神经系统中的受体功能和发现新的亚型选择性药物至关重要。我们将通过讨论它们的亚基组成、药理学和定位来综述啮齿动物脑亚型，并在可能的情况下将它们与其他哺乳动物物种或鸡脑中存在的相同亚型进行比较。特别是，我们将集中于存在于视觉通路（视网膜、上级丘和外侧膝状核）中的nAChR，其中神经元表达大多数（如果不是全部）nAChR亚单位。除了主要的α 4 β 2和α 7 nAChR亚型外，视觉通路选择性地表达具有复杂亚基组成的亚型。通过从对照组和病变大鼠，野生型和nAChR亚基敲除小鼠获得的组织上的配体结合和免疫沉淀和免疫纯化实验，我们已经定性和定量地鉴定，并鉴定了含有多达四个不同亚基的多个复杂的天然亚型。(C)2007年由Elsevier Inc.出版
Neuronal cholinergic nicotinic receptors (nAChRs) are a heterogeneous class of cationic channels that are widely distributed in the nervous system that have specific functional and pharmacological properties. They consist of homologous subunits encoded by a large multigene family, and their opening is physiologically controlled by the acetylcholine neurotransmitter or exogenous ligands such as nicotine. Their biophysical and pharmacological properties depend on their subunit composition, which is therefore central to understanding receptor function in the nervous system and discovering new subtype-selective drugs.We will review rodent brain subtypes by discussing their subunit composition, pharmacology and localisation and, when possible, comparing them with the same subtypes present in the brain of other mammalian species or chick.In particular, we will focus on the nAChRs present in the visual pathway (retina, superior colliculus and nucleus geniculatus lateralis), in which neurons express most, if not all, nAChR subunits. In addition to the major alpha 4 beta 2 and alpha 7 nAChR subtypes, the visual pathway selectively expresses subtypes with a complex subunit composition. By means of ligand binding and immunoprecipitation and immunopurification experiments on tissues obtained from control and lesioned rats, and wild-type and nAChR subunit knockout mice, we have qualitatively and quantitatively identified, and pharmacologically characterised, the multiple complex native subtypes containing up to four different subunits. (C) 2007 Published by Elsevier Inc.