H pylori is an inprobable cause of hypergastrinaemia.
H pylori infection is reported to cause hypergastrinaemia, in
patients with duodenal ulcers, which is reversed by eradication (1).
Furthermore gastric secretory function in these patients is said to be
disinhibited through the suppression of mucosal somatostatin (2).
We studied the release of gastrin from 1 cms pieces of human antral
mucosa, harvested immediately after delivery in the operating room of
resected specimens obtained from 78 patients who underwent gastric
resection, stripped of adherent muscularis and mounted in Ussing chambers
in such a way that luminal surfaces were perfused independently of serosal
surfaces. T"he amount of immunoreactive gastrin (IG) released during
stimulation with the luminal pH at 7.4 increased linearly with time and
stopped abruptly when the luminal pH was lowered to 2.5. The rate at which
IG was released by the same stimulus at pH 7.4 was linearly related to the
IG content in antral tissue (r = 0.66). The IG content in antral tissue
increased during stimulation (10.05 +/- 2.09 to 19.77 +/- 3.38 pmol/mg
tissue protein, P less than 0.03)"(3).
The specimens were also examined by a histopathologist. All had
evidence of gastrititis there being a rough correlation between the
severity of the gastritis and the gastrin responses. The highest by far
were from a piece of antral mucosa harvested during placement of a
Celestin tube in a patient with inoperable oesophageal cancer. This piece
of mucosa had no evidence of gastritis. Clearly, therefore, the presence
of gastritis impairs the capacity for the syntheis and release of gastrin
from human antral mucosa.
We subsequently showed that luminal pH had reciprocal effects upon
gastrin and somatostatin release from antral mucosa obtained from
anaesthetized dogs, a rise in luminal pH from 2.5 to 7 stimulating gastrin
release and inhibiting somatostatin release (4). We then showed in healthy
human volunteers that the addition of somatostatin to fluid instilled in
to lumen of the stomach, with the pH clamped by intragastric titration,
"inhibited the rate of acid secretion as compared with placebo alone in
the control subjects (p < 0.025) without altering the concentration of
immunoreactive gastrin in the serum but reducing the concentration of
immunoreactive gastrin in gastric juice (p < 0.02)"(5).
These data suggest that the hypergastrinaemia and disinhibition
"through suppression of mucosal somatostatin" reported by Calam's group,
might have been the product of a elevation in intragastric pH associated
with the decreased capacity to secrete acid rather than an effect upon the
somatostatin cells themselves for in anything the gastritis caused by H
pylori should have reduced the capacity for both antral gastrin and
somatostatin synthesis and release. Whilst our data reflected changes in
hormone released into the lumen rather than from the serosal surface, this
is consistent with the anatomy of the gastrin G and somatosttin D cells
both of which communicate with the lumen with microvillous borders. It is
also consistent with the unpublished studies of one of my surgical
research fellows, Jim Palmer who hailed from Middlesex/UCH. In
constructing isolated antral pouches in dogs he showed that the
directional responses we had observed in vitro with both human and antral
mucosa also occurred in vivo.
Interpreting gastrin and somatostatin responses solely from changes
in circulating concentrations of the hormones and without knowing the
luminal pH or antral content and capacity for synthesis of new hormone is
an extremely hazardous exercise.
1. Levi S, Beardshall K, Swift I, Foulkes W, Playford R, Ghosh P,
Calam J. Antral Helicobacter pylori, hypergastrinaemia, and duodenal
ulcers: effect of eradicating the organism. BMJ. 1989 Dec
16;299(6714):1504-5
2. Moss SF, Legon S, Bishop AE, Polak JM, Calam J. Effect of
Helicobacter pylori on gastric somatostatin in duodenal ulcer disease.
Lancet. 1992 Oct 17;340(8825):930-2
3. Fiddian-Green RG, Vinik AI. The meaning of a gastrin response to a
test meal. Surgery. 1983 Dec;94(6):1038-42
4. Fink AS, Hedenbro JL, Vinik AI, Unger RH, Fiddian-Green RG. A
reciprocal relationship between the release of immunoreactive gastrin and
somatostatin-like immunoreactivity from canine antral mucosa in vitro.
Curr Surg. 1980 Jan-Feb;37(1):63-6.
5. Fiddian-Green RG, Pittenger G, Kothary P. Effect of luminal
somatostatin on acid secretion and gastrin release. Scand J
Gastroenterol. 1980;15(3):305-9.
N. F. Knight, R. G. Fiddian-Green, A. I. Vinik In vivo release of
gastrin into human gastric juice. British Journal of Surgery 1977, Volume
65 Issue 2, Pages 118 - 120
Rapid Response:
H pylori is an inprobable cause of hypergastrinaemia.
H pylori infection is reported to cause hypergastrinaemia, in
patients with duodenal ulcers, which is reversed by eradication (1).
Furthermore gastric secretory function in these patients is said to be
disinhibited through the suppression of mucosal somatostatin (2).
We studied the release of gastrin from 1 cms pieces of human antral
mucosa, harvested immediately after delivery in the operating room of
resected specimens obtained from 78 patients who underwent gastric
resection, stripped of adherent muscularis and mounted in Ussing chambers
in such a way that luminal surfaces were perfused independently of serosal
surfaces. T"he amount of immunoreactive gastrin (IG) released during
stimulation with the luminal pH at 7.4 increased linearly with time and
stopped abruptly when the luminal pH was lowered to 2.5. The rate at which
IG was released by the same stimulus at pH 7.4 was linearly related to the
IG content in antral tissue (r = 0.66). The IG content in antral tissue
increased during stimulation (10.05 +/- 2.09 to 19.77 +/- 3.38 pmol/mg
tissue protein, P less than 0.03)"(3).
The specimens were also examined by a histopathologist. All had
evidence of gastrititis there being a rough correlation between the
severity of the gastritis and the gastrin responses. The highest by far
were from a piece of antral mucosa harvested during placement of a
Celestin tube in a patient with inoperable oesophageal cancer. This piece
of mucosa had no evidence of gastritis. Clearly, therefore, the presence
of gastritis impairs the capacity for the syntheis and release of gastrin
from human antral mucosa.
We subsequently showed that luminal pH had reciprocal effects upon
gastrin and somatostatin release from antral mucosa obtained from
anaesthetized dogs, a rise in luminal pH from 2.5 to 7 stimulating gastrin
release and inhibiting somatostatin release (4). We then showed in healthy
human volunteers that the addition of somatostatin to fluid instilled in
to lumen of the stomach, with the pH clamped by intragastric titration,
"inhibited the rate of acid secretion as compared with placebo alone in
the control subjects (p < 0.025) without altering the concentration of
immunoreactive gastrin in the serum but reducing the concentration of
immunoreactive gastrin in gastric juice (p < 0.02)"(5).
These data suggest that the hypergastrinaemia and disinhibition
"through suppression of mucosal somatostatin" reported by Calam's group,
might have been the product of a elevation in intragastric pH associated
with the decreased capacity to secrete acid rather than an effect upon the
somatostatin cells themselves for in anything the gastritis caused by H
pylori should have reduced the capacity for both antral gastrin and
somatostatin synthesis and release. Whilst our data reflected changes in
hormone released into the lumen rather than from the serosal surface, this
is consistent with the anatomy of the gastrin G and somatosttin D cells
both of which communicate with the lumen with microvillous borders. It is
also consistent with the unpublished studies of one of my surgical
research fellows, Jim Palmer who hailed from Middlesex/UCH. In
constructing isolated antral pouches in dogs he showed that the
directional responses we had observed in vitro with both human and antral
mucosa also occurred in vivo.
Interpreting gastrin and somatostatin responses solely from changes
in circulating concentrations of the hormones and without knowing the
luminal pH or antral content and capacity for synthesis of new hormone is
an extremely hazardous exercise.
1. Levi S, Beardshall K, Swift I, Foulkes W, Playford R, Ghosh P,
Calam J. Antral Helicobacter pylori, hypergastrinaemia, and duodenal
ulcers: effect of eradicating the organism. BMJ. 1989 Dec
16;299(6714):1504-5
2. Moss SF, Legon S, Bishop AE, Polak JM, Calam J. Effect of
Helicobacter pylori on gastric somatostatin in duodenal ulcer disease.
Lancet. 1992 Oct 17;340(8825):930-2
3. Fiddian-Green RG, Vinik AI. The meaning of a gastrin response to a
test meal. Surgery. 1983 Dec;94(6):1038-42
4. Fink AS, Hedenbro JL, Vinik AI, Unger RH, Fiddian-Green RG. A
reciprocal relationship between the release of immunoreactive gastrin and
somatostatin-like immunoreactivity from canine antral mucosa in vitro.
Curr Surg. 1980 Jan-Feb;37(1):63-6.
5. Fiddian-Green RG, Pittenger G, Kothary P. Effect of luminal
somatostatin on acid secretion and gastrin release. Scand J
Gastroenterol. 1980;15(3):305-9.
N. F. Knight, R. G. Fiddian-Green, A. I. Vinik In vivo release of
gastrin into human gastric juice. British Journal of Surgery 1977, Volume
65 Issue 2, Pages 118 - 120
Competing interests:
None declared
Competing interests: No competing interests