Change search
ReferencesLink to record
Permanent link

Direct link
Substance P and the neurokinin-1 receptor in relation to eosinophilia in ulcerative colitis
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Kirurgi.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
2005 (English)In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 26, no 5, 799-814 p.Article in journal (Refereed) Published
Abstract [en]

Substance P (SP) has been implicated in the pathophysiology of ulcerative colitis (UC) and it has been suggested that blocking of its effect would be advantageous in this disease. Eosinophils have also been implicated in the pathophysiology of UC. In the present study, specimens from the sigmoid colon of UC patients were investigated by the use of antisera against SP and the neurokinin-1 receptor (NK-1R) and staining for demonstration of eosinophils. The degrees of SP innervation and NK-1R immunoreaction, as well as the levels of eosinophil infiltration, varied between different patients. Interestingly, NK-1R immunoreaction in the epithelium was often seen to be the most marked where there were numerous eosinophils in the underlying mucosa and where the mucosa showed a marked morphologic derangement. The observations suggest that there are marked fluctuations in effects of SP and eosinophils during the disease. The infiltrating eosinophils may be involved in the destruction of the mucosal tissue. Furthermore, for the majority of cases where there is marked derangement of the mucosa, it is apparent that there is an upregulation of the NK-1 receptor in the epithelium in parallel with the infiltration of the eosinophils.

Place, publisher, year, edition, pages
2005. Vol. 26, no 5, 799-814 p.
Keyword [en]
adult, aged, colitis, ulcerative/metabolism/pathology, colon/pathology, eosinophilia/pathology, female, humans, intestinal mucosa/immunology, male, middle aged, muscle, smooth/immunology, myenteric plexus/immunology, nerve fibers/immunology, receptors, neurokinin-1/analysis/metabolism, substance P/analysis/metabolism
URN: urn:nbn:se:umu:diva-6041DOI: 10.1016/j.peptides.2004.12.018PubMedID: 15808910OAI: diva2:145709
Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2011-08-31Bibliographically 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

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Jönsson, MariaNorrgård, ÖrjanForsgren, Sture
By organisation
In the same journal

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 59 hits
ReferencesLink to record
Permanent link

Direct link