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

Abstract : 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 alpha4beta2 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00161479
Contributor : Yolande Meunier <>
Submitted on : Tuesday, July 10, 2007 - 5:11:57 PM
Last modification on : Wednesday, September 23, 2020 - 4:33:20 AM

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Pierre-Jean Corringer, Jérôme Sallette, Jean-Pierre Changeux. Nicotine enhances intracellular nicotinic receptor maturation: a novel mechanism of neural plasticity?. Journal of Physiology - Paris, Elsevier, 2006, 99 (2-3), pp.162-71. ⟨10.1016/j.jphysparis.2005.12.012⟩. ⟨pasteur-00161479⟩

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