Gotti Cecilia, Zoli Michele, Clementi Francesco
CNR, Institute of Neuroscience, Cellular and Molecular Pharmacology, Department of Medical Pharmacology and Center of Excellence on Neurodegenerative Diseases, University of Milan, 20129 Milan, Italy.
Trends Pharmacol Sci. 2006 Sep;27(9):482-91. doi: 10.1016/j.tips.2006.07.004. Epub 2006 Jul 31.
Neuronal nicotinic acetylcholine receptors comprise a heterogeneous class of cationic channels that is present throughout the nervous system. These channels are involved both in physiological functions (including cognition, reward, motor activity and analgesia) and in pathological conditions such as Alzheimer's disease, Parkinson's disease, some forms of epilepsy, depression, autism and schizophrenia. They are also the targets of tobacco-smoking effects and addiction. Neuronal nicotinic acetylcholine receptors are pentamers of homomeric or heteromeric combinations of alpha (alpha2-alpha10) and beta (beta2-beta4) subunits, which have different pharmacological and biophysical properties and locations in the brain. The lack of subtype-specific ligands and the fact that many neuronal cells express multiple subtypes initially hampered the identification of the different native nicotinic acetylcholine receptor subtypes, but the increasing knowledge of subtype composition and roles will be of considerable interest for the development of new and clinically useful nicotinic acetylcholine receptor ligands.
神经元烟碱型乙酰胆碱受体由一类异质性阳离子通道组成，存在于整个神经系统中。这些通道既参与生理功能（包括认知、奖赏、运动活动和镇痛），也涉及病理状况，如阿尔茨海默病、帕金森病、某些形式的癫痫、抑郁症、自闭症和精神分裂症。它们也是吸烟效应和成瘾的靶点。神经元烟碱型乙酰胆碱受体是由α（α2-α10）和β（β2-β4）亚基的同源或异源组合构成的五聚体，这些亚基在大脑中具有不同的药理学和生物物理学特性及位置。缺乏亚型特异性配体以及许多神经元细胞表达多种亚型这一事实，最初阻碍了不同天然烟碱型乙酰胆碱受体亚型的鉴定，但对亚型组成和作用的了解不断增加，将对开发新的、具有临床应用价值的烟碱型乙酰胆碱受体配体具有重要意义。
