神经元烟碱型胆碱能受体亚型的发现之路。
The road to discovery of neuronal nicotinic cholinergic receptor subtypes.
作者信息
Collins Allan C, Salminen Outi, Marks Michael J, Whiteaker Paul, Grady Sharon R
机构信息
Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA.
出版信息
Handb Exp Pharmacol. 2009(192):85-112. doi: 10.1007/978-3-540-69248-5_4.
The discovery that mammalian brain expresses the mRNAs for nine different nicotinic cholinergic receptor subunits (alpha2-alpha7, beta2-beta4) that form functional receptors when expressed in Xenopus laevis oocytes suggests that many different types of nicotinic cholinergic receptors (nAChRs) might be expressed in the mammalian brain., Using an historical approach, this chapter reviews some of the progress made in identifying the nAChR subtypes that seem to play a vital role in modulating dopaminergic function. nAChR subtypes that are expressed in dopamine neurons, as well as neurons that interact with dopamine neurons (glutamatergic, GABAergic), serve as the focus of this review. Subjects that are highlighted include the discovery of a low affinity alpha4beta2* nAChR, the identity of recently characterized alpha6* nAChRs, and the finding that these alpha6* receptors have the highest affinity for receptor activation of any of the native receptors that have been characterized to date. Topics that have been ignored in other recent reviews of this area, such as the discovery and potential importance of alternative transcripts, are presented along with a discussion of their potential importance.
哺乳动物大脑表达九种不同烟碱型胆碱能受体亚基（α2-α7、β2-β4）的mRNA，这些亚基在非洲爪蟾卵母细胞中表达时可形成功能性受体，这一发现表明哺乳动物大脑中可能表达多种不同类型的烟碱型胆碱能受体（nAChRs）。本章采用历史的方法，回顾了在鉴定似乎在调节多巴胺能功能中起关键作用 的nAChR亚型方面取得的一些进展。在多巴胺能神经元以及与多巴胺能神经元相互作用的神经元（谷氨酸能、γ-氨基丁酸能）中表达的nAChR亚型是本综述的重点。重点讨论的主题包括低亲和力α4β2* nAChR的发现、最近鉴定的α6* nAChRs的特性，以及这些α6*受体对迄今为止已鉴定的任何天然受体的受体激活具有最高亲和力的发现。本领域其他近期综述中忽略的主题（如可变转录本的发现及其潜在重要性）也将呈现，并对其潜在重要性进行讨论。
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