Nicotine enhances intracellular nicotinic receptor maturation: A novel mechanism of neural plasticity?

被引:64
作者
Corringer, PJ [1 ]
Sallette, J [1 ]
Changeux, JP [1 ]
机构
[1] Inst Pasteur, Unit Receptor & Cognit, F-75724 Paris 15, France
关键词
nicotine; nicotinic receptor; up-regulation; pharmacological chaperon;
D O I
10.1016/j.jphysparis.2005.12.012
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Nicotine addiction, the primary cause of tobacco consumption, is mediated through nicotine binding to brain nicotinic acetylcholine receptor (nAChRs). Upon chronic exposure, nicotine elicits a cascade of events, starting with nAChR activation and desensitization, followed by a long term up-regulation that corresponds to an increase in the number of the high affinity nAChRs, a paradoxical process that occurs in the brain of smokers. Recent investigation of the maturation and trafficking of the major brain alpha 4 beta 2 nAChR demonstrates that up-regulation is initiated in the endoplasmic reticulum soon after protein translation. The data thus far accumulated provide evidence that nicotine elicits up-regulation by promoting maturation of nAChR precursors that would otherwise be degraded. This maturational enhancer" action of nicotine probably contributes to the long term effect of chronic nicotine.. and suggests a novel mechanism of neuronal plasticity through an yet unknown endogenous substance which would modulate the receptor expression under physiological conditions. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:162 / 171
页数:10
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