Gotti C, Riganti L, Vailati S, Clementi F
CNR, Institute of Neuroscience, Section of Cellular and Molecular Pharmacology, Department of Medical Pharmacology, University of Milan, Via Vanvitelli 32, 20129 Milano, Italy.
Curr Pharm Des. 2006;12(4):407-28. doi: 10.2174/138161206775474486.
Neuronal nicotinic receptors (nAChRs) are a heterogeneous family of ion channels differently expressed in the nervous system where, by responding to the endogenous neurotransmitter acetylcholine, they contribute to a wide range of brain activities and influence a number of physiological functions. Over recent years, the application of newly developed molecular and cellular biological techniques has made it possible to correlate the subunit composition of nAChRs with specific nicotine-elicited behaviours, and refine some of the in vivo physiological functions of nAChR subtypes. The major new findings are the widespread expression of nAChRs, outside the nervous system, their specific and complex organisation, and their relevance to normal brain function. Moreover, the combination of clinical and basic research has better defined the involvement of nAChRs in a growing number of nervous pathologies other than degenerative diseases. However, there are still only a limited number of nicotinic-specific drugs and, although some nicotinic agonists have an interesting pharmacology, their clinical use is limited by undesirable side effects. Some selective nicotinic ligands have recently been developed and used to explore the complexity of nAChR subtype structure and function in the expectation that they will become rational therapeutic alternatives in a number of neurodegenerative, neuropsychiatric and neurological disorders. In this review, we will discuss the molecular basis of brain nAChR structural and functional diversity mainly in pharmacological and biochemical terms, and summarise current knowledge concerning the newly discovered drugs used to classify the numerous receptor subtypes and treat the brain diseases in which nAChRs are involved.
神经元烟碱型受体（nAChRs）是一类异质性离子通道家族，在神经系统中表达各异。通过对内源性神经递质乙酰胆碱作出反应，它们参与多种脑活动，并影响许多生理功能。近年来，新开发的分子和细胞生物学技术的应用使得将nAChRs的亚基组成与特定的尼古丁诱发行为相关联，并完善nAChR亚型的一些体内生理功能成为可能。主要的新发现包括nAChRs在神经系统之外的广泛表达、它们特定而复杂的组织形式以及它们与正常脑功能的相关性。此外，临床研究与基础研究的结合更好地明确了nAChRs在除退行性疾病之外越来越多的神经病理学中的作用。然而，目前烟碱特异性药物的数量仍然有限，尽管一些烟碱激动剂具有有趣的药理学特性，但其临床应用受到不良副作用的限制。最近已经开发出一些选择性烟碱配体，并用于探索nAChR亚型结构和功能的复杂性，期望它们将成为治疗多种神经退行性、神经精神性和神经性疾病的合理替代疗法。在这篇综述中，我们将主要从药理学和生物化学角度讨论脑nAChR结构和功能多样性的分子基础，并总结有关用于分类众多受体亚型和治疗涉及nAChRs的脑部疾病的新发现药物的当前知识。
