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Investigation of peptidergic and nitrergic innervation of the human antrum Smith, Valerie C.
Abstract
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.
Item Metadata
Title |
Investigation of peptidergic and nitrergic innervation of the human antrum
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
1999
|
Description |
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.
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Extent |
10089178 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-06-15
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0099368
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
1999-05
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Item Media
Item Citations and Data
Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.