Nicotine enhances intracellular nicotinic receptor maturation: a novel mechanism of neural plasticity?
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.
Corringer
Pierre-Jean
PJ
Unit of receptor and Cognition, Pasteur Institute, 25 rue du docteur Roux, 75724 Paris Cedex 15, France. pjcorrin@pasteur.fr
Sallette
Jérôme
J
Changeux
Jean-Pierre
JP
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects*; D008954:Models, Biological; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
D021122:Protein Subunits; D011978:Receptors, Nicotinic; D009538:Nicotine