Gotti Cecilia, Moretti Milena, Gaimarri Annalisa, Zanardi Alessio, Clementi Franceso, Zoli Michele
CNR, Institute of Neuroscience, Cellular and Molecular Pharmacology, Department of Medical Pharmacology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy.
Biochem Pharmacol. 2007 Oct 15;74(8):1102-11. doi: 10.1016/j.bcp.2007.05.023. Epub 2007 Jun 2.
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 alpha4beta2 and alpha7 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.
神经元胆碱能烟碱受体（nAChRs）是一类异质性阳离子通道，广泛分布于具有特定功能和药理学特性的神经系统中。它们由一个大型多基因家族编码的同源亚基组成，其开放在生理上受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其亚基组成，因此这对于理解神经系统中的受体功能以及发现新的亚型选择性药物至关重要。我们将通过讨论其亚基组成、药理学和定位来回顾啮齿动物脑内的亚型，并尽可能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，我们将重点关注视觉通路（视网膜、上丘和外侧膝状体核）中存在的nAChRs，其中神经元表达了大部分（如果不是全部）nAChR亚基。除了主要的α4β2和α7 nAChR亚型外，视觉通路还选择性地表达具有复杂亚基组成的亚型。通过对从对照和损伤大鼠以及野生型和nAChR亚基敲除小鼠获得的组织进行配体结合、免疫沉淀和免疫纯化实验，我们已经定性和定量地鉴定了多种复杂的天然亚型，并对其进行了药理学表征，这些亚型包含多达四种不同的亚基。
