Targeting α-7 nicotinic acetylcholine receptor in the enteric nervous system: a cholinergic agonist prevents gut barrier failure after severe burn injury

Am J Pathol. 2012 Aug;181(2):478-86. doi: 10.1016/j.ajpath.2012.04.005. Epub 2012 Jun 8.


We have previously shown that vagal nerve stimulation prevents intestinal barrier loss in a model of severe burn injury in which injury was associated with decreased expression and altered localization of intestinal tight junction proteins. α-7 Nicotinic acetylcholine receptor (α-7 nAchR) has been shown to be necessary for the vagus nerve to modulate the systemic inflammatory response, but the role of α-7 nAchR in mediating gut protection remained unknown. We hypothesized that α-7 nAchR would be present in the gastrointestinal tract and that treatment with a pharmacological agonist of α-7 nAchR would protect against burn-induced gut barrier injury. The effects of a pharmacological cholinergic agonist on gut barrier integrity were studied using an intraperitoneal injection of nicotine 30 minutes after injury. Intestinal barrier integrity was examined by measuring permeability to 4-kDa fluorescein isothiocyanate-dextran and by examining changes in expression and localization of the intestinal tight junction proteins occludin and ZO-1. Nicotine injection after injury prevented burn-induced intestinal permeability and limited histological gut injury. Treatment with nicotine prevented decreased expression and altered localization of occludin and ZO-1, as seen in animals undergoing burn alone. Defining the interactions among the vagus nerve, the enteric nervous system, and the intestinal epithelium may lead to development of targeted therapeutics aimed at reducing gut barrier failure and intestinal inflammation after severe injury.

MeSH terms

  • Animals
  • Burns / complications
  • Burns / metabolism
  • Burns / pathology*
  • Caco-2 Cells
  • Cells, Cultured
  • Cholinergic Agonists / administration & dosage
  • Cholinergic Agonists / pharmacology*
  • Enteric Nervous System / drug effects
  • Enteric Nervous System / metabolism*
  • Enteric Nervous System / pathology*
  • Epithelial Cells / metabolism
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / innervation*
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / pathology*
  • Humans
  • Inflammation / complications
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neuroglia
  • Nicotine / administration & dosage
  • Nicotine / pharmacology
  • Protein Transport / drug effects
  • Receptors, Nicotinic / metabolism*
  • Tight Junction Proteins / drug effects
  • Tight Junction Proteins / metabolism
  • alpha7 Nicotinic Acetylcholine Receptor


  • Cholinergic Agonists
  • Chrna7 protein, human
  • Chrna7 protein, mouse
  • Receptors, Nicotinic
  • Tight Junction Proteins
  • alpha7 Nicotinic Acetylcholine Receptor
  • Nicotine