Structural and functional diversity of native brain neuronal nicotinic receptors

Biochem Pharmacol. 2009 Oct 1;78(7):703-11. doi: 10.1016/j.bcp.2009.05.024. Epub 2009 May 27.

Abstract

Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channels present in the central and peripheral nervous systems, that are permeable to mono- and divalent cations. They share a common basic structure but their pharmacological and functional properties arise from the wide range of different subunit combinations making up distinctive subtypes. nAChRs are involved in many physiological functions in the central and peripheral nervous systems, and are the targets of the widely used drug of abuse nicotine. In addition to tobacco dependence, changes in their number and/or function are associated with neuropsychiatric disorders, ranging from epilepsy to dementia. Although some of the neural circuits involved in the acute and chronic effects of nicotine have been identified, much less is known about which native nAChR subtypes are involved in specific physiological functions and pathophysiological conditions. We briefly review some recent findings concerning the structure and function of native nAChRs, focusing on the subtypes identified in the mesostriatal and habenulo-interpeduncular pathways, two systems involved in nicotine reinforcement and withdrawal. We also discuss recent findings concerning the effect of chronic nicotine on the expression of native subtypes.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism*
  • Humans
  • Neural Pathways / metabolism
  • Neurons / metabolism*
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology
  • Protein Conformation
  • Protein Multimerization
  • Protein Subunits / biosynthesis
  • Protein Subunits / chemistry
  • Protein Subunits / physiology
  • Receptors, Nicotinic / biosynthesis
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / physiology*
  • Tobacco Use Disorder / metabolism
  • Tobacco Use Disorder / physiopathology

Substances

  • Nicotinic Agonists
  • Protein Subunits
  • Receptors, Nicotinic
  • Nicotine