Ileitis alters neuronal and enteroendocrine signalling in guinea-pig distal colon

Jennifer R O'Hara ¹, Alan E Lomax ², Gary M Mawe ³ and Keith A Sharkey ^1*

¹ University of Calgary, Canada
² Queen's University, Canada
³ University of Vermont, United States

^* To whom correspondence should be addressed. E-mail: ksharkey{at}ucalgary.ca.

Accepted 17 August 2006

Abstract

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 TNBS-induced ileitis on the properties of submucosal neurons, enteroendocrine cells and epithelial physiology of the distal colon of guinea-pigs.

Results: Three days following administration of TNBS, when overt inflammation was restricted to the ileum, the properties of enteric neurons were altered. Submucosal AH neurons in the colon were hyperexcitable and had reduced afterhyperpolarizations. S neurons received larger fast and slow EPSPs, due to an increase in non-cholinergic synaptic transmission. Similar changes in inflamed regions have been reported to be mediated by PGE2. Despite the absence of inflammation in the colon, we found increased colonic PGE2 content in animals with ileitis. Ileitis also increased the number of colonic 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 Isc 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 GI tract alters the cellular components of enteric reflex circuits in distant, non-inflamed regions in ways that are similar to changes seen at sites of active inflammation. These changes appear to underlie altered function in non- involved regions during episodes of intestinal inflammation.

Keywords: enteric nervous system, intestinal inflammation, ion transport, serotonin, submucosal plexus

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