Helicobacter pylori and gastric acid: An intimate and reciprocal relationship

Helicobacter pylori (Hp) is the main cause of gastritis, peptic ulcer disease and gastric cancer. There are still unanswered questions related to the interaction between Hp and man, like what determines the susceptibility for the initial infection and the mechanisms for the carcinogenic effect. The initial infection seems to require a temporal gastric hypoacidity. For Hp to survive in the gastric mucous layer, some acidity is necessary. Hp itself is probably not directly carcinogenic. Only when inducing oxyntic mucosal inflammation and atrophy with hypoacidity, Hp predisposes for gastric cancer. Gastrin most likely plays a central role in the Hp pathogenesis of duodenal ulcer and gastric cancer

Effect of the histamine-2 agonist impromidine on stem cell proliferation of rat oxyntic mucosa

Background: The trophic effect of gastrin on the histamine-containing enterochromaffin-like cell is pronounced but on the stem cell of the oxyntic mucosa it is only modest. In the rat, gastrin stimulates acid secretion mainly by releasing histamine from enterochromaffin-like cells. This study was designed to test the hypothesis that the trophic effect of gastrin on stem cells is also mediated by histamine released from the enterochromaffin-like cell. Methods: We stimulated rats with the histamine-2 agonist impromidine. Impromidine, 0.2mg/h, was given for 2 days by subcutaneously implanted osmotic minipumps, and the trophic effect on stem cells was assessed by incorporation of tritiated thymidine. Results: The plasma gastrin concentrations were 33.9 (9.4) pM and 27.3 (6.0) pM, and the stem cell labelling index values were 5.92 (1.94) and 8.09 (3.78) in the controls and impromidine-stimulated animals, respectively (mean value (SD)). These differences were not statistically significant. Conclusion: The present study provides no evidence that histamine-2 receptors mediate a trophic effect on the stem cell of the rat oxyntic mucosa. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Hypergastrinemia is associated with an increased risk of gastric adenocarcinoma with proximal location:A prospective population-based nested case-control study

The incidence of proximal gastric adenocarcinoma is increasing among younger adults. Rodent models have shown that hypergastrinemia causes carcinogenesis in the proximal stomach. The aim of our study was therefore to assess if hypergastrinemia was associated with an increased risk of developing gastric adenocarcinoma also in humans. A prospective population‐based nested case‐control study within the Nord‐Trøndelag Health Study (HUNT) cohort, Norway, was used to assess this association. Serum was collected from 78 962 participants in 1995 to 1997 and 2006 to 2008. In the cohort, 181 incident gastric adenocarcinoma cases were identified from the Norwegian Cancer and Patient Registries through 2015 and matched with 359 controls. The risk of gastric adenocarcinoma was compared between participants with prediagnostic hypergastrinemia (>60 pmol/L) and normal serum gastrin (≤60 pmol/L). Logistic regression provided odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for body mass index, tobacco smoking and comorbidity. Hypergastrinemia was associated with increased risk of gastric adenocarcinoma overall (OR 2.2, 95% CI 1.4‐3.4) and in particular for gastric adenocarcinoma with proximal location (OR 6.1, 95% CI 2.7‐13.8), but not with gastric adenocarcinoma with distal location (OR 1.7, 95% CI 0.9‐3.4). Moreover, hypergastrinemia was associated with an increased risk of gastric adenocarcinoma of intestinal histological type (OR 3.8, 95% CI 1.8‐7.9), but not for diffuse histological type (OR 1.6, 95% CI 0.7‐3.7). In conclusion, hypergastrinemia was associated with an increased risk of proximal and intestinal type gastric adenocarcinoma

Somatostatin-receptor 2 (sst(2))-mediated effects of endogenous somatostatin on exocrine and endocrine secretion of the rat stomach

1. Somatostatin is a potent inhibitor of gastric acid secretion. Its effects are mediated through five specific receptor subtypes (sst(1–5)), of which sst(2) is dominant on the enterochromaffin-like (ECL) cell and the parietal cell. To study the paracrine mechanisms of somatostatin, the sst(2)-specific antagonist PRL-2903 was used. 2. Effects of PRL-2903 on acid secretion and release of histamine were studied in the totally isolated, vascularly perfused rat stomach. Further, the release of histamine and gastrin after bombesin, alone and in combination with PRL-2903, were studied. Results are presented as mean±standard error of the mean (s.e.m.). 3. PRL-2903 concentration-dependently increased the venous histamine concentration from basal 55.6±7.5 to 367±114 nM at 50 μM PRL-2903. With 10 μM PRL-2903, venous histamine output increased from baseline 6.2±0.5 to 20.9±4.9 nmol h(−1); P=0.008. The combination of 520 pM gastrin and 10 μM PRL-2903 increased venous histamine output from 41.7±7.3 nmol h(−1) with gastrin alone to 95.2±9.8 nmol h(−1); P=0.016. Further, 10 μM PRL-2903 increased acid output from baseline 8.5±1.8 to 37.4±11 μmol h(−1); P=0.017. When combined with 10 μM ranitidine, PRL-2903 did not significantly stimulate acid secretion. Bombesin/PRL-2903 increased venous histamine concentration from 50.4±14.8 to 292±64.2 nM; P=0.008, and gastrin concentration from 38.6±13.1 to 95.8±20.3 pM; P=0.037. 4. Endogenous somatostatin exerts a continuous restraint on histamine and gastrin release from the gastric mucosa and significantly reduces baseline acid secretion