gastrin-releasing-peptide and Helicobacter-Infections

Gastrin is a pro-proliferative, anti-apoptotic hormone with a central role in acid secretion in the gastric mucosa and a long-standing association with malignant progression in transgenic mouse models. However, its exact role in human gastric malignancy requires further validation. Gastrin expression is tightly regulated by two closely associated hormones, somatostatin and gastrin-releasing peptide, and aspects of their interaction may be deregulated during progression to gastric adenocarcinoma. Furthermore, agonists and antagonists of the receptors for all three hormones have shown modest clinical efficacy against gastric adenocarcinoma, which might provide useful information on the future combined use of these agents.

Topics: Animals; Antineoplastic Agents, Hormonal; Apoptosis; Cancer Vaccines; Cell Differentiation; Cell Movement; Cell Transformation, Neoplastic; Gastrin-Releasing Peptide; Gastrins; Gene Expression Regulation, Neoplastic; Helicobacter Infections; Humans; Mice; Neoplasm Invasiveness; Neoplasms, Experimental; Neovascularization, Pathologic; Precancerous Conditions; Risk Factors; Somatostatin; Stomach Neoplasms

Helicobacter pylori (H pylori) raises serum gastrin but it is unclear whether this stimulates increased acid secretion. Gastrin mediated acid secretion and plasma gastrin after the intravenous infusion of gastrin releasing peptide was studied in nine H pylori negative and nine H pylori positive healthy volunteers, and in 11 duodenal ulcer patients. Nine of the last group were re-examined one month after eradication of H pylori. The median acid output (mmol/h) to gastrin releasing peptide (40 pmol/kg/h) in the H pylori positive healthy volunteers was 15.1 (range 3.3-38.3), which was three times that of the H pylori negative healthy volunteers (median = 5.5, range 1.0-9.0) (p < 0.02). The median acid output in the duodenal ulcer patients with H pylori was 37 (range 8.5-57), which was > six times that of the H pylori negative healthy volunteers. Eradication of H pylori in the duodenal ulcer patients lowered their acid secretion by a median of 66% (range 30%-80%) (p < 0.01) and to values equivalent to the H pylori positive healthy volunteers. The pepsin output in response to gastrin releasing peptide followed the same pattern as the acid output. The median plasma gastrin concentrations during gastrin releasing peptide were similar in the H pylori positive duodenal ulcer patients (150 ng/l, range 95-400) and H pylori positive healthy volunteers (129 ng/l, range 23-420) and both were appreciably higher than H pylori negative healthy volunteers (60 ng/l, range 28-135) (p < 0.005 for each). Eradication of H pylori lowered the plasma gastrin in the duodenal ulcer patients to values equivalent to the H pylori negative healthy volunteers. These findings show a threefold increase in acid secretion in H pylori positive healthy volunteers that is explained by H pylori induced hypergastrinaemia and a sixfold increase in acid secretion in the duodenal ulcer patients that is explained by the combination of H pylori induced hypergastrinaemia and an exaggerated acid response to stimulation by gastrin. Eradicating H pylori lowers gastrin mediated acid secretion by 66% in duodenal ulcer patients as a result of the resolution of the hypergastrinaemia. Increased gastrin mediated acid secretion seems to be the key factor in the pathophysiology of duodenal ulceration and explains the role of H pylori infection in the disorder.

Topics: Amoxicillin; Anti-Bacterial Agents; Basal Metabolism; Breath Tests; Carbon Radioisotopes; Duodenal Ulcer; Female; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Infusions, Intravenous; Male; Metronidazole; Organometallic Compounds; Pepsin A; Peptides; Time Factors; Urea

Helicobacter pylori eradication reduces the recurrence of duodenal ulcers. It is unclear why duodenal ulcers rarely recur in the absence of reinfection with H. pylori or NSAID treatment.. Basal, gastrin-releasing peptide- and pentagastrin-stimulated peak acid outputs in patients with ulcer relapse after H. pylori eradication were measured, and compared with patients without ulcer relapse after H. pylori eradication.. Pentagastrin-stimulated peak acid output was significantly higher in H. pylori-positive patients with duodenal ulcers than in H. pylori-negative controls, and fell significantly after H. pylori eradication. In H. pylori-negative patients with recurrent duodenal ulcers, pentagastrin-stimulated peak acid output was significantly higher than in controls and similar to H. pylori-positive patients with duodenal ulcers.. These findings suggest that duodenal ulcer relapse after eradication of H. pylori may be related to high pentagastrin-stimulated peak acid output. In this subset of patients with duodenal ulcers, maintenance anti-secretory treatment may be necessary to prevent relapse.

Topics: Adult; Duodenal Ulcer; Gastric Acid; Gastrin-Releasing Peptide; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pentagastrin; Peptides; Recurrence

Topics: Duodenal Ulcer; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Humans; Peptides

Topics: Duodenal Ulcer; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Humans; Parietal Cells, Gastric; Peptides

Previous study showed that duodenal ulcer (DU) patients infected with Helicobacter pylori (H. pylori) have increased basal and pentagastrin- or GRP-induced gastric acid secretion and that these disturbances reversed fully after eradication of H. pylori. This study was designed to compare the gastric acid secretory profile, plasma gastrin levels and growth factors (EGF and TGF alpha) expression in gastric mucosa in DU patients with those in atrophic gastritis patients before and six months after verified eradication of H. pylori. In DU patients, basal and stimulated (GRP and pentagastrin) gastric acid secretion was significantly higher than in healthy controls. Six months following the eradication of H. pylori with triple therapy (omeprazole+clarithromycin+amoxicillin), this secretion returned to normal value. In contrast, in patients with atrophic gastritis, such eradication of H. pylori resulted in a significant increase in basal and pentagastrin- and GRP-stimulated acid secretion. Mucosal expression of immunoreactive EGF and TGF alpha was significantly enhanced in H. pylori positive DU and atrophic gastritis patients but this elevation disappeared or was markedly decreased 6 months upon the eradication of H. pylori. We conclude that 1) H. pylori infection is accompanied both in DU and atrophic gastritis patients by an enhanced plasma gastrin and increased mucosal expression of EGF and TGF alpha, 2) basal and GRP-induced acid secretion is significantly elevated in DU, whereas that in atrophic gastritis patients is greatly reduced, and 3) the H. pylori eradication restores gastric acid and plasma gastrin release as well as the mucosal expression of growth factors in DU and atrophic gastritis.

Topics: Adult; Duodenal Ulcer; Epidermal Growth Factor; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Transforming Growth Factor alpha

Dyspeptic symptoms frequently recur rapidly after withdrawal of H2 antagonists, and this might be related to rebound acid hypersecretion. We have studied this phenomenon in healthy volunteers with and without Helicobacter pylori infection.. Basal and gastrin-releasing peptide (GRP) (40 pmol/kg/h) stimulated acid output, and gastrin concentration were measured in 18 healthy volunteers (nine were H. pylori positive). Studies were performed before and at 60 h and 10 days after completion of a 60-day course of ranitidine 300 mg nocte.. In the H. pylori-negative healthy volunteers, basal acid output increased by a median of 137% 2 days after stopping ranitidine therapy compared with pretreatment values (p = 0.01) and returned to pretreatment values by day 10 posttreatment. Their GRP-stimulated acid output increased by a median of 108% 2 days post ranitidine (p < 0.01) and remained slightly increased at day 10. In H. pylori-positive healthy volunteers, basal acid output increased by a median of 96% 2 days after ranitidine therapy ceased (p < 0.01) and returned to pretreatment values by day 10 posttreatment. Their GRP-stimulated acid output also increased by a median of 56% 2 days posttreatment and returned to pretreatment values by day 10. The increase in acid output both basal and in response to GRP was not accompanied by any rise in gastrin concentration in either the H. pylori-positive or -negative subjects.. Ranitidine therapy is associated with marked rebound hypersecretion of acid, and this may contribute to rapid resurgence of symptoms after therapy has been discontinued.

Topics: Anti-Ulcer Agents; Bombesin; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Gastrointestinal Hormones; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Male; Peptides; Ranitidine; Time Factors

The mechanism(s) by which sucralfate heals duodenal ulcers remains unclear. The aim of this study was to determine the effect of sucralfate on Helicobacter pylori infection and on the accompanying hypersecretion of gastric acid the infection induces in patients with duodenal ulcer.. Basal and gastrin-releasing peptide (GRP) stimulated gastrin release and acid secretion. H. pylori density, gastric urease activity, and severity of gastritis were studied in patients with duodenal ulcer who were positive for H. pylori before, during, and after 4 weeks' treatment with sucralfate (2 g twice daily).. The density of H. pylori decreased by 70% during sucralfate treatment and returned to the pretreatment level after discontinuation of therapy. This suppression of H. pylori infection was accompanied by an 80% decrease in gastric urease activity. GRP-stimulated plasma gastrin concentrations, GRP-stimulated acid output, and basal acid output all decreased by approximately 50% during sucralfate therapy and returned to pretreatment levels after treatment was discontinued.. These findings indicate that sucralfate markedly suppresses H. pylori infection and the accompanying hypersecretion of acid the infection induces in patients with duodenal ulcer. These effects are likely to be important mechanisms by which the drug promotes duodenal ulcer healing.

Topics: Adult; Aged; Anti-Ulcer Agents; Breath Tests; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Peptides; Stomach; Sucralfate; Urease

Topics: Duodenal Ulcer; Gastric Acid; Gastrin-Releasing Peptide; Helicobacter Infections; Helicobacter pylori; Humans; Peptides

Helicobacter pylori infection and duodenal ulcer disease are firmly correlated. However, the bacteria do mainly colonize the antrum, indicating an indirect pathogenic mechanism. The aim of this study was to test a concept claiming that H. pylori infection of the antrum selectively blocks normal inhibitory reflex pathways to gastrin and parietal cells.. The effect of antral distention was studied on gastric acid secretion stimulated by pentagastrin and on gastrin release stimulated by gastrin-releasing peptide in H. pylori-infected and noninfected patients with and without duodenal ulcer disease, as well as after eradication of the bacteria.. The inhibitory effect on gastric acid secretion induced by antral distention was absent in H. pylori-infected patients irrespective of whether or not they had duodenal ulcer disease. The inhibitory mechanism was restituted in 8 of 10 patients within 9 months after successful eradication of H. pylori infection. Similar results were obtained in studies on gastrin release.. H. pylori infection blocks normal, physiological inhibitory mechanisms from the antrum to both the gastrin cells and to the parietal cell region, resulting in increased gastrin release and impaired inhibition of gastric acid secretion, which will probably lead to an increased duodenal acid load as a general prerequisite for the development of duodenal ulcer disease.

Topics: Adult; Aged; Duodenal Ulcer; Female; Gastric Acid; Gastric Dilatation; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Parietal Cells, Gastric; Pentagastrin; Peptides; Pyloric Antrum; Stomach Diseases

Patients with duodenal ulcer (DU) have high basal (BAO) and peak (PAO) acid outputs. The effect of Helicobacter pylori eradication on these variables is unclear.. To discover if gastric acid hypersecretion in patients with DU is caused by H pylori.. BAO, gastrin releasing peptide (GRP), and pentagastrin stimulated PAO in 10 H pylori negative controls, and in 10 H pylori positive patients with DU was measured before and six months after H pylori eradication. H pylori status was determined by histology, culture, and by the 13C-urea breath test. After collecting a 30 minute basal aspirate, GRP 40 pmol/kg/h was infused for 45 minutes, and after a 30 minute washout, pentagastrin 6 micrograms/kg was injected intramuscularly.. Basal and stimulated acid output (PAOGRP and PAOPg) were significantly higher in H pylori positive DU than in H pylori negative controls. Six months after H pylori eradication, basal and stimulated acid outputs were all significantly lower than before H pylori eradication.. This study has shown that BAO, PAOGRP, and PAOPg are higher in H pylori positive DU than in H pylori negative controls. All decreased significantly six months after H pylori eradication, to fall within the range of controls. These results are compatible with a hypothesis that acid hypersecretion in duodenal ulcer disease is caused by H pylori infection.

Topics: Adult; Case-Control Studies; Duodenal Ulcer; Female; Gastric Acid; Gastric Juice; Gastrin-Releasing Peptide; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pentagastrin; Peptides

The mechanism by which Helicobacter pylori predisposes to duodenal ulcers (DUs) remains unclear. The aim of this study was to investigate the effect of the infection on acid secretion.. Acid output was examined basally and in response to gastrin-releasing peptide (GRP) and gastrin in healthy volunteers with and without H. pylori infection and in patients with DUs before and after eradication of the infection.. Compared with H. pylori-negative healthy volunteers, patients with DUs with H. pylori had the following abnormalities of acid secretion: (1) threefold increase in basal acid output, (2) sixfold increase in acid response to GRP, (3) increased maximal acid response to exogenous gastrin, (4) increased ratio of basal acid output to maximal gastrin-stimulated output, and (5) increased ratio of maximal GRP-stimulated acid output to maximal gastrin-stimulated output. All of these abnormalities resolved fully after H. pylori eradication except for increased maximal acid output to gastrin, which was unchanged. Infected healthy volunteers showed a threefold increase in acid response to GRP that resolved after eradication of H. pylori infection.. These disturbances in acid secretion caused by H. pylori infection are consistent with impaired inhibitory control and are likely to be relevant to the mechanism by which the infection predisposes to DU.

Topics: Amoxicillin; Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Drug Therapy, Combination; Duodenal Ulcer; Gastric Acid; Gastric Mucosa; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Linear Models; Male; Metronidazole; Organometallic Compounds; Peptides; Reproducibility of Results

Acid secretion in response to gastrin releasing peptide (GRP) is increased six-fold in Helicobacter pylori positive duodenal ulcer (DU) patients and threefold in H pylori positive healthy volunteers, and this fully resolves after eradication of the infection. This study was undertaken to determine whether a proportion of H pylori positive patients with non-ulcer dyspepsia (NUD) have an acid secretion disturbance similar to DU patients. Basal and GRP stimulated gastrin concentrations and acid output were examined in 25 H pylori positive NUD patients and the results compared with those of 25 H pylori positive healthy volunteers, 25 H pylori negative healthy volunteers, and 25 H pylori positive DU patients. Compared with the H pylori negative healthy volunteers, GRP stimulated gastrin was increased approximately three fold in each of the three infected groups. GRP stimulated acid secretion (median, range) was higher in the H pylori positive NUD patients (29.6 mmol/h (5.2-46.5)) (p < 0.005) than in the H pylori positive healthy volunteers (19.0 (1.0-38.3)) (p < 0.001) or H pylori negative healthy volunteers (6.3 (2.8-20.9)) (p < 0.0001). The H pylori positive NUD patients, however, had lower acid output than the DU patients (39.1 (17.9-64)) (p < 0.005). These findings are consistent with approximately 50% of the NUD patients having a similar disturbance of GRP stimulated acid secretion to DU patients.

Topics: Adolescent; Adult; Duodenal Ulcer; Dyspepsia; Female; Gastric Acid; Gastrin-Releasing Peptide; Gastrins; Gastrointestinal Hormones; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Peptides; Stimulation, Chemical

Topics: Amoxicillin; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Gastric Acid; Gastrin-Releasing Peptide; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Peptides

Helicobacter pylori increases gastrin release in duodenal ulcer patients. This may be through disruption or changes in the mucus layer affecting the access of luminal stimulants to gastrin releasing cells. The effect of suppressing H pylori on gastrin release stimulated by a non-luminal stimulus, gastrin releasing peptide (GRP), was examined. Eleven patients with active duodenal ulcer disease and colonised with H pylori received an intravenous infusion of GRP (2.9 pmol/kg/minute for 30 minutes) and the plasma gastrin response was measured. Basal and peak pentagastrin stimulated acid output were also determined. Patients were treated with tripotassium dicitratobismuthate (De-Nol) and metronidazole to suppress H pylori and the tests were repeated. Suppression of H pylori decreased plasma gastrin concentrations during GRP infusion, but acid output was not affected. Chromatographic analysis of the forms of gastrin in plasma showed a significant fall in gastrin 17, the predominant form found in the gastric antrum. Gastrin 34 did not fall significantly. This study shows that suppression of H pylori decreases the hypergastrinaemia caused by the nonluminal stimulant, GRP, mainly via decreasing gastrin 17.

Topics: Adult; Duodenal Ulcer; Female; Gastrin-Releasing Peptide; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Peptides; Secretory Rate