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Presence of mRNA for VIP and Substance P and presence of VPAC1 and NK-1 receptor expressions in the colonic epithelium of man: changed pattern in ulcerative colitis
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. (Sture Forsgren)
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. (Sture Forsgren)
(English)Manuscript (Other academic)
Abstract [en]

 

The neuropeptides vasoactive intestinal peptide (VIP) and substance P (SP) are considered to be important in ulcerative colitis (UC). It is generally assumed that the main source of VIP and SP in the intestine is the innervation. There is no information concerning whether or not they are produced by cells in the epithelial layer. Concerning UC, there is also a lack of information concerning the VIP-receptor VPAC1 in the epithelium. In the present study, UC and non-UC colon was examined concerning expressions of VIP, SP, VPAC1 and the SP-preferred receptor, neurokinin-1 (NK-1R). Both immunohistochemistry and in situ hybridization were applied. mRNA expression for both VIP and SP were observed in the epithelium. The mRNA reactions were seen in normal and little/moderately affected mucosa. There were very marked VPAC1 immunoreactions in the epithelium, in non-UC mucosa and in little affected UC mucosa. A decrease in VPAC1 immunoreactions was noted in the epithelium in markedly affected UC mucosa. Existence of VIP immunoreaction, VIP mRNA, VPAC1 immunoreaction, SP mRNA, NK-1R immunoreaction and Substance P receptor (TACR1) mRNA was shown for cells in lamina propria and submucosa. The present study shows unexpectedly that mRNA for both VIP and SP are not only expressed in neuronal perikarya and lamina propria and submucosal cells but also in the colonic epithelium, and that marked changes in VPAC1 receptor expressions occur for this layer in severe UC. It is tentative to speculate that autocrine/paracrine VIP and SP effects may occur within the epithelium. The decrease in VPAC1 receptor reactions seen in severely UC affected mucosa may be a drawback for the intestinal function.

 

Keyword [en]
colitis, colonic epithelium, SP, VIP, VPAC1, NK-1 receptor
National Category
Cell and Molecular Biology
Research subject
Human Anatomy
Identifiers
URN: urn:nbn:se:umu:diva-19945OAI: oai:DiVA.org:umu-19945DiVA: diva2:207792
Available from: 2009-03-13 Created: 2009-03-12 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.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1248
Keyword
ulcerative colitis, neuropeptides, substance P, VIP, non-neuronal cholinergic system
National Category
Cell and Molecular Biology Surgery
Research subject
Human Anatomy
Identifiers
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)
Opponent
Supervisors
Available from: 2009-03-13 Created: 2009-03-12 Last updated: 2010-04-15Bibliographically approved

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