Roles of nicotinic acetylcholine receptor β subunits in function of human α4‐containing nicotinic receptors
Roles of nicotinic acetylcholine receptor β subunits in function of human α4‐containing nicotinic receptors
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烟碱乙酰胆碱受体β亚基在人类含α4烟碱受体功能中的作用
DOI：
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
R. Lukas
中科院分区：
文献类型：
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作者：
Jie Wu;Qiang Liu;Kewei Yu;Jun Hu;Y. Kuo;Marsha Segerberg;P. S. St john;R. Lukas
天然表达的烟碱乙酰胆碱受体（nAChR）含有α4亚基（α4*-nAChR）和β2亚基（α4β2-nAChR），是哺乳动物大脑中最丰富的高亲和力尼古丁结合位点之一。β4亚基也在涉及尼古丁和尼古丁依赖行为反应的几个脑区中丰富表达并与α4亚基共定位。因此，α4β4-nAChR也可能存在并发挥重要的功能作用。在这项研究中，确定了人SH-EP 1上皮细胞中从头异源表达的人α4β2-和α4β4-nAChR的特性。通过人α4β4-nAChR介导的全细胞电流的振幅是通过人α4β2-nAChR介导的全细胞电流的1.4倍，并且表现出慢得多的急性脱敏和功能衰退。烟碱激动剂诱导峰值全细胞电流反应，通常对α4β4-nAChR的功能效力高于对α4β2-nAChR的功能效力。野靛碱和洛贝林是α4β4-nAChR的完全激动剂，但仅是α4β2-nAChR的部分激动剂。然而，除六甲铵外，烟碱拮抗剂对功能性α4β2-和α4β4-nAChR的亲和力相当。在正保持电位下，全细胞电流响应显示α4β2-nAChR的内向整流比α4β4-nAChR强。总的来说，这些发现表明，人nAChR β2或β4亚基可以与α4亚基联合收割机产生两种形式的α4*-nAChR，具有独特的生理和药理学特征。α4*-nAChR的多样性与神经系统功能、疾病和尼古丁依赖有潜在的相关性。
Naturally expressed nicotinic acetylcholine receptors (nAChR) containing α4 subunits (α4*‐nAChR) in combination with β2 subunits (α4β2‐nAChR) are among the most abundant, high‐affinity nicotine binding sites in the mammalian brain. β4 subunits are also richly expressed and colocalize with α4 subunits in several brain regions implicated in behavioural responses to nicotine and nicotine dependence. Thus, α4β4‐nAChR also may exist and play important functional roles. In this study, properties were determined of human α4β2‐ and α4β4‐nAChR heterologously expressed de novo in human SH‐EP1 epithelial cells. Whole‐cell currents mediated via human α4β4‐nAChR have ∼4‐fold higher amplitude than those mediated via human α4β2‐nAChR and exhibit much slower acute desensitization and functional rundown. Nicotinic agonists induce peak whole‐cell current responses typically with higher functional potency at α4β4‐nAChR than at α4β2‐nAChR. Cytisine and lobeline serve as full agonists at α4β4‐nAChR but are only partial agonists at α4β2‐nAChR. However, nicotinic antagonists, except hexamethonium, have comparable affinities for functional α4β2‐ and α4β4‐nAChR. Whole‐cell current responses show stronger inward rectification for α4β2‐nAChR than for α4β4‐nAChR at a positive holding potential. Collectively, these findings demonstrate that human nAChR β2 or β4 subunits can combine with α4 subunits to generate two forms of α4*‐nAChR with distinctive physiological and pharmacological features. Diversity in α4*‐nAChR is of potential relevance to nervous system function, disease, and nicotine dependence.
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DOI：
10.1523/jneurosci.19-21-09298.1999
发表时间：
1999
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Jacob3rd,P