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Investigation of peptidergic and nitrergic innervation of the human antrum

University of British Columbia

Immunocytochemical studies were carried out to determine the normal peptidergic and nitrergic innervation, as well as the cellular expression of the neurokinin 1 receptor in the human antrum. Antral tissue was obtained from 36 multiple organ donors and processed for immunocytochemical studies using antibodies/antisera for vasoactive intestinal polypeptide, nitric oxide synthase, calcitonin gene-related peptide, substance P, gastrin releasing peptide, the neurokinin 1 receptor, c-kit, s100, fibronectin, von Willebrand factor, gastrin, somatostatin and serotonin. The significant findings from these studies are as follows: first, the human antrum has a prominent submucosal plexus containing nerve fibers and neurons which showed immunoreactivity for a majority of the neuromodulators investigated; second, the distribution of NOS was extended to include mucosal fibers innervating the surface of the antral glands; third, within the mucosal layer vasoactive intestinal polypeptide, nitric oxide synthase and gastrin releasing peptide immunoreactive nerve fibers were observed to be in close apposition to gastrin cells; fourth, within the human antrum somatostatin immunoreactivity was confined to endocrine cells in the mucosal layer. In order to determine the targets of the neuromodulators in the human antrum knowledge of the location of their respective receptors is required. Due to the species specificity of receptor sequences these studies were confined to the neurokinin 1 receptor. Two antibodies for the NK-1 r were utilized. Western blot analysis of the two antibodies showed that both antibodies detected a band at 46 kDa, the molecular weight of the NK-1r. Both antibodies immunostained cell bodies in the submucosal and myenteric plexuses. Many of these cell bodies were often surrounded by SP-IR nerve fibers. Endothelial cells lining the major blood vessels were also immunostained with both the NK-1r antibodies. However, the monoclonal antibody, mAb12, was found to immunostain numerous other cell types. Double labeling experiments demonstrated that c-kit-IR interstitial cells of Cajal in the circular muscle were also NK-1r-IR as were gastrin-IR endocrine cells in the mucosal layer. In the human antrum, the peptidergic and nitrergic innervation are considerably different from that reported in other animals. The presence of abundant mucosal innervation along with a well defined large submucosal plexus suggests that, in the human antrum, gastric functions may be regulated by alternate mechanisms than those proposed from animal investigations. In addition, the distribution of the NK-1r is also significantly expanded and different from that reported in other species suggesting that the mechanism of physiological regulation of the human antrum cannot be extrapolated from information obtained in animal studies. In conclusion these data strongly suggest that human antral gastrin cells will be regulated by vasoactive intestinal polypeptide, nitric oxide, gastrin releasing peptide and substance P.

Thesis/Dissertation

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2009-06-15

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http://hdl.handle.net/2429/9143

Physiology

University of British Columbia

UBCV

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