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Neuroendocrine peptide levels in the gastrointestinal tract of mice after unilateral cervical vagotomy
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
2000 (English)In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 88, no 1-3, 15-20 p.Article in journal (Refereed) Published
Abstract [en]

The effects of left and right unilateral cervical vagotomy on the content of several neuroendocrine peptides were studied in different parts of the murine gastrointestinal tract, known to receive vagal innervation. The neuroendocrine peptides investigated were secretin, gastric inhibitory peptide (GIP), gastrin, motilin, peptide YY (PYY), somatostatin, substance P, VIP, neurotensin, neuropeptide Y (NPY), and galanin. The neuroendocrine peptide concentration was affected after both left and right vagotomy, and that the changes in the concentrations of the neuroendocrine peptide levels occurred in all the gastrointestinal segments investigated, namely antrum, small and large intestine. However, these changes varied, depending on which side was vagotomized and the interval after vagotomy. It is concluded that the vagus nerve had an important impact on the neuroendocrine system in the murine gut. It is suggested, furthermore that the contradictory results obtained earlier on the effect of vagotomy on the gastrointestinal peptides may depend on differences in the vagotomy methods used and on differences in observation time after vagotomy.

Place, publisher, year, edition, pages
2000. Vol. 88, no 1-3, 15-20 p.
Keyword [en]
Neuroendocrine peptides; Mouse; Gastrointestinal tract; Radioimmunoassay; Vagotomy
National Category
Neurology Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:umu:diva-73346DOI: 10.1016/S0167-0115(99)00107-XPubMedID: 10706947OAI: oai:DiVA.org:umu-73346DiVA: diva2:631084
Available from: 2013-06-20 Created: 2013-06-20 Last updated: 2017-12-06Bibliographically approved
In thesis
1. An experimental study on the interaction between the neuro-endocrine and immune systems in the gastrointestinal tract
Open this publication in new window or tab >>An experimental study on the interaction between the neuro-endocrine and immune systems in the gastrointestinal tract
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The mucosa lining of the gastrointestinal (GI) tract is in immediate contact with food nutrients to allow a rapid and efficient digestion and absorption and at the same time protects against the incessant risk of attack from pathogenic microbes. Maintenance of normal physiological activities in the GI tract is dependent on a number of regulatory interactions between the nervous, endocrine, and immune systems, as well as environmental and genetic factors. Impaired nervous and/or endocrine systems may endanger mucosal immunity and thereby increase the susceptibility to infectious agents, elicit an uncontrolled inflammatory response and cause a failure of immune surveillance. Aberrant immune functions may also lead to an apparent neuro-endocrine disturbance. A better understanding of the neuro-endocrine immunomodulation in the GI tract and its influence on the inflammatory process, therefore, will hold the promise of novel strategy to the treatment of immunologically and/or neuro-endocrinologically mediated diseases with the use of appropriate regulatory substances.

In this thesis, the neuro-endocrine system and its interaction(s) with the immune system in the GI tract were studied using mouse models combined with immunological and molecular biological techniques (e.g. immunomorphometry, quantitative RT-PCR). The following could be concluded:

1) Vagus nerves are fundamental to the enteric neuro-endocrine system. Frequencies and morphology of several types of endocrine cells and tissue levels of neuropeptides along the GI tract were significantly changed by vagotomy.

2) The local enteric neuro-endocrine system may have important influences on bowel inflammation. Polypeptide YY (PYY) cells and tissue levels of PYY, substance P (SP) and vasoactive intestinal polypeptide (VIP) were dramatically decreased in the inflamed colon of IL-2-/- mice as compared to the health IL-2+/- and IL-2+/+ controls.

3) Notably, IL-2 deficiency per se caused marked neuro-endocrine alterations in the gut. The volume densities of enteroglucagon-, serotonin-cells and SP-, VIP- or total myenteric nerves were lower in IL-2+/- and IL-2-/- mice as compared to the wild type. The normally occurring age related neuro-endocrine changes were also absent in mice with no (IL-2-/- mice) or reduced levels of IL-2 (IL-2+/- mice).

4) VIP generally exerted immunosuppressive effects. The magnitude of the effect differed with T cells in different compartments. Proliferation in response to polyclonal T cell activators was significantly down-regulated by VIP in splenic but not intestinal T lymphocytes. Cytokine production was also affected. Expression of mRNAs for interleukin-2 (IL-2), the Th1 cytokine interferon-γ (IFN-γ), and the Th2 cytokine IL-4 in activated small intestinal lamina propria and splenic T cells was inhibited by VIP in a dose dependent manner. In contrast, the inhibitory action of VIP on cytokine production was much less pronounced in intestinal intraepithelial T lymphocytes in which only IFN-γ mRNA expression was reduced.

5) The effects of VIP on lymphocytes are most probably receptor mediated. Intestinal T cells were shown to bind VIP. T cells in both small and large intestine as well as spleen had the mRNA expression for VIP-receptor 1. It was expressed in all T cell subtypes tested i.e. CD4+ , CD8+, and CD4-CD8-CD3+ cells. Interestingly, VIP receptor 2 mRNA was only found in CD8+ lymphocytes of small intestine. This indicates a functional diversity and specificity of VIP in immune modulation.

6) SP may act as an autocrine as well as a paracrine immunoregulatory agent in intestinal mucosa. T cells from both the epithelium and lamina propria of small and large intestine were found to produce SP and at the same time express the SP receptor.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2001. 62 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 719
Keyword
gastrointestinal tract, neuro-endocrine system, substance P, vasoactive intestinal polypeptide, vagus nerves, mucosal immune system, T lymphocytes, cytokines, inflammation, mouse
National Category
Neurology Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-73364 (URN)91-7191-994-5 (ISBN)
Public defence
2001-03-15, Astrid Fagreussalen A103, Norrlands universitetssjukhus, Umeå, 09:00
Opponent
Available from: 2013-06-20 Created: 2013-06-20 Last updated: 2013-06-20Bibliographically approved

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