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Presence of a marked nonneuronal cholinergic system in human colon: study of normal colon and colon in ulcerative colitis
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
2007 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 13, no 11, 1347-1356 p.Article in journal (Other academic) Published
Abstract [en]

BACKGROUND: The body has not only a neuronal but also a nonneuronal cholinergic system. Both systems are likely to be very important, particularly in inflammatory conditions. The patterns and importance of the nonneuronal cholinergic system in patients with ulcerative colitis (UC) are largely unknown.

METHODS: The colons of UC and non-UC patients were examined for expression patterns of choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), and the muscarinic receptor of the M(2) subtype.

RESULTS: ChAT and VAChT immunoreactions and mRNA reactions for ChAT were detected in epithelial and endocrine cells, in cells in the lamina propria, and in blood vessel walls. Furthermore, a marked M(2) immunoreaction was noted for epithelium, blood vessel walls, and smooth musculature. ChAT and VAChT immunoreactions were significantly higher in endocrine and epithelial cells, respectively, in non-UC mucosa than in UC mucosa. On the other hand, there was a tendency toward higher M(2) levels in epithelium of UC patients.

CONCLUSIONS: There is a pronounced nonneuronal cholinergic system in the colon, which has previously been ignored when discussing cholinergic influences in UC. Furthermore, it is evident that certain changes in the nonneuronal cholinergic system occur in response to inflammation/derangement in UC. Cholinergic effects in the colon can be considered to be related not only to nerve-related effects but also to effects of acetylcholine from nonneuronal local cells. Thus, the recently discussed phenomenon of a "cholinergic antiinflammatory pathway" in the intestine may have a pronounced nonneuronal component.

Place, publisher, year, edition, pages
2007. Vol. 13, no 11, 1347-1356 p.
Keyword [en]
adult, case-control studies, choline O-acetyltransferase/analysis, colitis, ulcerative/metabolism/pathology, colon/metabolism/pathology, female, humans, inflammation/metabolism, male, middle aged, receptor, muscarinic M2/analysis, tissue distribution, vesicular acetylcholine transport proteins/analysis
URN: urn:nbn:se:umu:diva-8145DOI: 10.1002/ibd.20224PubMedID: 17663429OAI: diva2:147816
Available from: 2008-01-15 Created: 2008-01-15 Last updated: 2010-06-24Bibliographically approved
In thesis
1. The neuronal and non-neuronal substance P, VIP and cholinergic systems in the colon in ulcerative colitis
Open this publication in new window or tab >>The neuronal and non-neuronal substance P, VIP and cholinergic systems in the colon in ulcerative colitis
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. Neuropeptides, especially vasoactive intestinal peptide (VIP) and substance P (SP), have long been considered to play key roles in UC. Among other effects, these neuropeptides have trophic and growth-modulating as well as wound-healing effects. Furthermore, whilst VIP has anti-inflammatory properties, SP has pro-inflammatory effects. It is generally assumed that the main source of SP and VIP in the intestine is the tissue innervation. It is not known whether or not they are produced in the epithelial layer. The details concerning the expressions of their receptors in UC are also, to a great extent, unclear. Apart from the occurrence of peptidergic systems in the intestine, there are also neuronal as well as non-neuronal cholinergic systems. The pattern concerning the latter is unknown with respect to UC.

The studies in this thesis aimed to investigate the expression of SP and VIP and their major receptors (NK-1R and VPAC1) in UC colon, compared to non-UC colon. The main emphasis was devoted to the epithelium. A second aim was to examine for levels of these neuropeptides in blood plasma in UC. Another aim was to examine for the non-neuronal cholinergic system in UC, thus, to investigate whether there is acetylcholine production outside nerves in the UC colon. Methods used in the thesis were immunohistochemistry, in situ hybridization, enzyme immunosorbent assay, and in vitro receptor autoradiography.

For the first time, mRNA for VIP and SP has here been found in the colonic epithelium. That was especially noted in UC mucosa showing a rather normal morphology, and in non-UC mucosa. Marked derangement of the mucosa was found to lead to a distinct decrease in VIP binding, and also a decrease in the expression level of VIP receptor VPAC1 in the epithelium. In general, there was an upregulation of the SP receptor NK-1R in the epithelium when the mucosa was deranged. The plasma levels of SP and VIP were higher for UC patients compared to healthy controls. There were marked correlations between the levels of the peptides in plasma, their levels in the mucosa and the degree of mucosal derangement/inflammation. A pronounced nonneuronal cholinergic system was found in both UC and non-UC colon. Certain changes occurred in this system in response to inflammation/derangement in UC. The present study shows unexpectedly that expressions for VIP and SP are not only related to the nerve structures and the inflammatory cells. The downregulation of VPAC1 expression, and the tendencies of upregulation of NK-1R expression levels when there is marked tissue derangement, may be a drawback for the intestinal function. The study also shows that there is a marked release of neuropeptides to the bloodstream in parallel with a marked derangement of the mucosa in UC. The cholinergic effects in the UC colon appear not only to be associated with nerverelated effects, but also effects of acetylcholine produced in local non-neuronal cells. The thesis shows that local productions for not only acetylcholine, but also SP and VIP, occur to a larger extent than previously considered.

Place, publisher, year, edition, pages
Umeå: Institutionen för integrativ medicinsk biologi, 2009. 62 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1248
ulcerative colitis, neuropeptides, substance P, VIP, non-neuronal cholinergic system
National Category
Cell and Molecular Biology Surgery
Research subject
Human Anatomy
urn:nbn:se:umu:diva-19946 (URN)978-91-7264-731-2 (ISBN)
Public defence
2009-04-03, BiA 201, Biologihuset, Umeå, 09:00 (Swedish)
Available from: 2009-03-13 Created: 2009-03-12 Last updated: 2010-04-15Bibliographically approved

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Norrgård, OrjanForsgren, Sture
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