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Chapter 9 (page 34)
Chapter 9
Regulatory Peptides
For a brief historical review of the regulatory peptides, one is indebted to Royston et al
(l978) and others. It was pointed out that Solcia and his colleagues (l967) described
endocrine-like cells in the gastric "antrum" which were argyrophilic, but non-argentaffin
in quality. The next year McGuigan (l968), by means of an immunofluorescent
technique, identified gastrin in cells of the antral mucosa, which he named G cells.
Bussolati and Pearse (l970), using immunofluorescent and silver techniques, showed that
these two types of cell were the same.
G cells belong to the APUD cell line; the technique of immunocytochemistry shows the
precise localization of the cells in the walls of the gastrointestinal tract. Individual cells
contain secretory granules in the basal part of the cytoplasm, whereas the Golgi complex
is supranuclear. In the pyloric mucosal zone most of the cells extend to the lumen in a
pyramidal way, with tufts of microvilli at the apex; these probably act as receptor sites.
Secreted peptides are demonstrated by radioimmunoassay of tissue extracts.
The following regulatory peptides appear to be among the more important in the present
context.
Edkins (1906) showed that an extract of pyloric mucosa administered intravenously
stimulated secretion of gastric acid and pepsinogen; he suggested that the active
principle was of hormonal origin and named it gastrin. It was soon apparent that this
action was similar to that of histamine, and many authorities considered gastrin and
histamine to be the same substance. As pointed out by Dockray (l978), nearly 60 years of
uncertainty about the existence, nature and specificity of the antral hormone gastrin, and
its relationship to histamine, followed. This was resolved when Gregory and Tracy (l96l,
l964) isolated two related heptadecapeptides from hog antral mucosa, which proved to be
gastrin. It was shown to occur in highest concentration in the pyloric mucosal zone,
where its concentration was 500 times higher than in the corpus of the stomach
(McGuigan l968).
Gastrin producing G cells originate from neuroectoderm together with other cells of the
APUD series. They have a clear appearance, are piriform in shape and located in the mid
and deep zones of the pyloric mucosal glands; electronmicroscopy shows that they
possess microvilli extending into the lumen and that secretory granules are present in the
basal parts of the cells. This organisation allows for secretion of hormone into the
bloodsteam in response to luminal stimuli (Dockray l978). Normally there are
approximately half a million G cells per cmª in the stomach in man, amounting to a total
of approximately 10 million G cells (Mortensen l980).
Synthesis of gastrin I and II occurs predominantly in the G cells of the pyloric mucosal
zone; less important sources are G cells in the duodenum, D cells in the islands of
Langerhans in the pancreas, and isolated G cells in the proximal acid producing region of
the fornix and body of the stomach. Some authorities hold that normally G cells do not
occur in the oxyntic zone of the stomach; they may however, be present in pathological
conditions (Stave and Brandtzaeg l976).
While G cells are interspersed among the more frequent mucus producing cells, the
question arises whether their spatial distribution is equal to that of the pyloric mucosal
zone; are G cells found throughout the pyloric mucosa, or are they confined to certain
areas of this zone? Stave and Brandtzaeg (l976) pointed out that there were few
quantitative data on the actual G cell mass of the stomach at that time; however,
variations in the numbers of antral G cells had been reported in relation to pathological
states. By means of immunohistochemical methods these authors attempted a systematic
mapping of the numerical distribution of G cells in the human stomach and duodenum in
specimens resected for peptic ulcer. In a small series (8 gastric ulcer cases and 8 cases of
duodenal ulcer with uraemia), no G cells were found in the oxyntic zone of the stomach.
A low number occurred in the transitional zone at the proximal border of the antrum
(Comment: The term "antrum" was not defined, but appeared to be equated with the
pyloric mucosal zone). In the gastric ulcer group no significant difference was found
between the numbers of G cells at various levels of the "antrum"; in the cases of
duodenal ulcer with uraemia there was a statistically significant increase in the number of
G cells from the proximal to the distal part of the "antrum". The first part of the
duodenum contained considerably fewer G cells than the "antrum", and the numbers in
the duodenum were virtually equal in the two groups.
In a second and larger series of cases, Stave and Brandtzaeg (l978) determined the antral
density, mucosal distribution and total mass of G cells in gastric resection specimens.
The series of 42 cases consisted of 12 cases of gastric ulcer, 14 cases of duodenal ulcer
with uremia, 11 cases of duodenal ulcer without uremia, and 5 cases of gastric carcinoma.
Immuno-reactive G cells were not seen in the oxyntic zone of the stomach in any of the
cases, and low numbers occurred in the transitional zone along the proximal border of the
pyloric antrum. The first part of the duodenum contained only a fifth to an eighth of the
number in the "distal antrum". (The distal antrum was now said to be the area extending
proximally from the pylorus for a distance of 3.0cm). In the duodenal ulcer group, as
well as in the group of duodenal ulcer with uraemia, and the gastric carcinoma group, the
density of G cells increased from the proximal to the distal part of the antrum; in the
group of gastric ulceration the overall density in various parts of the antrum remained the
same.
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