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

J Physiol Paris. Mar-May 2006;99(2-3):162-71. doi: 10.1016/j.jphysparis.2005.12.012. Epub 2006 Feb 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Humans
  • Intracellular Space / drug effects*
  • Models, Biological
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Nicotine / pharmacology*
  • Protein Biosynthesis / drug effects*
  • Protein Biosynthesis / physiology
  • Protein Subunits / metabolism
  • Receptors, Nicotinic / physiology*
  • Up-Regulation / drug effects

Substances

  • Protein Subunits
  • Receptors, Nicotinic
  • Nicotine