Ileitis alters neuronal and enteroendocrine signalling in guinea pig distal colon.
OBJECTIVE
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 after hyperpolarisations. 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 E(2) 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.


CONCLUSIONS
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.
O'Hara
Jennifer R
JR
Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta T2N 4N1, Canada.
Lomax
Alan E
AE
Mawe
Gary M
GM
Sharkey
Keith A
KA
D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D002452:Cell Count; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015232:Dinoprostone / Q000032:analysis; D019858:Enteroendocrine Cells / Q000473:pathology / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006168:Guinea Pigs; D007079:Ileitis / Q000473:pathology / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014302:Trinitrobenzenesulfonic Acid; D014701:Veratridine / Q000494:pharmacology
D018721:Muscarinic Agonists; D018723:Bethanechol; D005576:Colforsin; D012701:Serotonin; D014701:Veratridine; D014302:Trinitrobenzenesulfonic Acid; D015232:Dinoprostone