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Ileitis alters neuronal and enteroendocrine signalling in guinea pig distal colon
  1. Jennifer R O’Hara1,*,
  2. Alan E Lomax1,*,
  3. Gary M Mawe2,
  4. Keith A Sharkey1
  1. 1Institute for Infection, Immunity and Inflammation, Hotchkiss Brain Institute, Department of Physiology and Biophysics, University of Calgary, Alberta T2N 4N1, Canada
  2. 2Department of Anatomy and Neurobiology, University of Vermont, Burlington, VT 05405, USA
  1. Correspondence to:
    Dr Keith Sharkey
    Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 4N1, Canada; ksharkey{at}


Background and aims: Intestinal inflammation alters neuronal and enteroendocrine signalling, leading to functional adaptations in the inflamed bowel. Human studies have reported functional alterations at sites distant from active inflammation. Our aims were to determine whether neuronal and enteroendocrine signalling are altered in the uninflamed colon during ileitis.

Methods: We used neurophysiological, immunohistochemical, biochemical and Ussing chamber techniques to examine the effect of 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced ileitis on the properties of submucosal neurones, enteroendocrine cells and epithelial physiology of the distal colon of guinea pigs.

Results: Three days after TNBS administration, when inflammation was restricted to the ileum, the properties of colonic enteric neurones were altered. Submucosal AH neurones were hyperexcitable and had reduced afterhyperpolarisations. S neurones received larger fast and slow excitatory postsynaptic potentials, due to an increase in non-cholinergic synaptic transmission. Despite the absence of inflammation in the colon, we found increased colonic prostaglandin E2 content in animals with ileitis. Ileitis also increased the number of colonic 5-hydroxytryptamine (5-HT)- and GLP-2-immunoreactive enteroendocrine cells. This was accompanied by an increase in stimulated 5-HT release. Functional alterations in epithelial physiology occurred such that basal short circuit current was increased and veratridine-stimulated ion transport was reduced in the colon of animals with ileitis.

Conclusion: Our data suggest that inflammation at one site in the gut alters the cellular components of enteric reflex circuits in non-inflamed regions in ways similar to those at sites of active inflammation. These changes underlie altered function in non-involved regions during episodes of intestinal inflammation.

  • AHP, afterhyperpolarising potential
  • AP, action potential
  • APD50, action potential duration at half maximal amplitude
  • EC, enterochromaffin cell
  • ENS, enteric nervous system
  • EPSPs, excitatory postsynaptic potentials
  • GI, gastrointestinal
  • GLP-2, glucagon-like peptide-2
  • 5-HT, 5-hydroxytryptaminel
  • IH, hyperpolarisation-activated non-selective cation conductance
  • IBD, inflammatory bowel disease
  • Isc, short circuit current
  • LT, low-threshold
  • MPO, myeloperoxidase
  • PD, potential difference
  • PGE2, prostaglandin E2
  • RMP, resting membrane potential
  • TNBS, 2,4,6-trinitrobenzene sulphonic acid
  • TTX, tetrodotoxin
  • enteric nervous system
  • intestinal inflammation
  • ion transport
  • serotonin
  • submucosal plexus

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  • * These authors contributed equally to this work.

  • Author’s current address: Gastrointestinal Diseases Research Unit, Queen’s University, Kingston, Ontario K7L 5G2, Canada.

  • Published Online First 24 August 2006

  • Grant support: This work was supported by an operating grant from the Crohn’s and Colitis Foundation of Canada (CCFC) (KS and GM), and by NIH grant DK62267 (GM). KS is an Alberta Heritage Foundation for Medical Research (AHFMR) Medical Scientist and the CCFC Chair in Inflammatory Bowel Disease Research. AL is the recipient of a Canadian Association of Gastroenterology/Astra Zeneca/Canadian Institutes of Health Research postdoctoral fellowship. JO’H is an AHFMR graduate scholar.

  • Competing interests: None.