Lindstrom J, Schoepfer R, Whiting P
Receptor Biology Laboratory, Salk Institute for Biological Studies, San Diego, CA 92138.
Mol Neurobiol. 1987 Winter;1(4):281-337. doi: 10.1007/BF02935740.
Nicotinic acetylcholine receptors on neurons are part of a gene family that includes nicotinic acetylcholine receptors on skeletal muscles and neuronal alpha bungarotoxin-binding proteins that in many species, unlike receptors, do not have an acetylcholine-regulated cation channel. This gene superfamily of ligand-gated receptors also includes receptors for glycine and gamma-aminobutyric acid. Rapid progress on neuronal nicotinic receptors has recently been possible using monoclonal antibodies as probes for receptor proteins and cDNAs as probes for receptor genes. These studies are the primary focus of this review, although other aspects of these receptors are also considered. In birds and mammals, there are subtypes of neuronal nicotinic receptors. All of these receptors differ from nicotinic receptors of muscle pharmacologically (none bind alpha bungarotoxin, and some have very high affinity for nicotine), structurally (having only two types of subunits rather than four), and, in some cases, in functional role (some are located presynaptically). However, there are amino acid sequence homologies between the subunits of these receptors that suggest the location of important functional domains. Sequence homologies also suggest that the subunits of the proteins of this family all evolved from a common ancestral protein subunit. The ligand-gated ion channel characteristic of this superfamily is formed from multiple copies of homologous subunits. Conserved domains responsible for strong stereospecific association of the subunits are probably a fundamental organizing principle of the superfamily. Whereas the structure of muscle-type nicotinic receptors appears to have been established by the time of elasmobranchs and has evolved quite conservatively since then, the evolution of neuronal-type nicotinic receptors appears to be in more rapid flux. Certainly, the studies of these receptors are in rapid flux, with the availability of monoclonal antibody probes for localizing, purifying, and characterizing the proteins, and cDNA probes for determining sequences, localizing mRNAs, expressing functional receptors, and studying genetic regulation. The role of nicotinic receptors in neuromuscular transmission is well understood, but the role of nicotinic receptors in brain function is not. The current deluge of data using antibodies and cDNAs is beginning to come together nicely to describe the structure of these receptors. Soon, these techniques may combine with others to better reveal the functional roles of neuronal nicotinic receptors.
神经元上的烟碱型乙酰胆碱受体是一个基因家族的一部分，该家族包括骨骼肌上的烟碱型乙酰胆碱受体以及神经元α-银环蛇毒素结合蛋白，在许多物种中，与受体不同，这些蛋白没有乙酰胆碱调节的阳离子通道。这个配体门控受体的基因超家族还包括甘氨酸和γ-氨基丁酸的受体。最近，利用单克隆抗体作为受体蛋白的探针以及cDNA作为受体基因的探针，神经元烟碱受体的研究取得了快速进展。这些研究是本综述的主要重点，不过也会考虑这些受体的其他方面。在鸟类和哺乳动物中，存在神经元烟碱受体的亚型。所有这些受体在药理学上（均不结合α-银环蛇毒素，有些对尼古丁具有非常高的亲和力）、结构上（只有两种亚基类型而非四种）以及在某些情况下在功能作用上（有些位于突触前）都与肌肉型烟碱受体不同。然而，这些受体的亚基之间存在氨基酸序列同源性，这表明了重要功能域的位置。序列同源性还表明，这个家族蛋白质的亚基均从一个共同的祖先蛋白质亚基进化而来。这个超家族的配体门控离子通道特征由同源亚基的多个拷贝形成。负责亚基强烈立体特异性结合的保守结构域可能是该超家族的一个基本组织原则。肌肉型烟碱受体的结构似乎在板鳃亚纲动物时期就已确立，此后进化得相当保守，而神经元型烟碱受体的进化似乎变化更快。当然，随着用于定位、纯化和表征蛋白质的单克隆抗体探针以及用于确定序列、定位mRNA、表达功能性受体和研究基因调控的cDNA探针的出现，对这些受体的研究也在迅速变化。烟碱受体在神经肌肉传递中的作用已得到充分理解，但在脑功能中的作用尚不清楚。目前利用抗体和cDNA产生的大量数据正开始很好地整合在一起，以描述这些受体的结构。很快，这些技术可能会与其他技术相结合，以更好地揭示神经元烟碱受体的功能作用。
