Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Altered gastrin expression associated with Helicobacter pylori infection may contribute to the pathogenesis of peptic ulcer disease or gastric cancer in man, but gastrin has not been investigated in a murine model of Helicobacter infection. C57BL/6 mice were inoculated with Helicobacter felis and examined after 4-21 weeks for G and D cell numbers, antral gastrin and somatostatin mRNA, and luminal pH. In H. felis-infected mice, gastrin mRNA declined at four and six weeks after infection to 57% and 23%, respectively, of uninfected control values. Concurrently, somatostatin mRNA showed no change at four weeks and a modest 25% decrease at six weeks after infection. Similar reductions were noted in G and D cell numbers, resulting in a decrease in the G/D cell ratio after mice were infected with H. felis. Infected animals also showed a loss of parietal and chief cells, and an increased gastric pH. H. felis infection in C57BL/6 mice leads to an early suppression of G cell number and gastrin mRNA. These changes precede an alteration in somatostatin cell number and mRNA and, coupled with reductions in parietal and chief cells, may contribute both to severe impairment of gastric acid output and the potential for carcinogenic processes.
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PMID:Altered gastrin regulation in mice infected with Helicobacter felis. 1096 8

The hypergastrinemia and hyperacidity associated with Helicobacter pylori infection has been explained by either a primary excess of gastrin or a lack of inhibitory influence by somatostatin (SOM). The objective of the present study was to compare the concentrations of fundic and antral SOM- and antral progastrin-derived peptides in nonulcer dyspepsia (NUD) subjects with and without H. pylori infection. Antral and fundic mucosal biopsies were extracted and assayed for SOM and gastrin amide, glycine-extended gastrin (gastrin gly), progastrin, and total gastrin. There was a significant sixfold reduction in antral SOM but no change in fundic SOM content in H. pylori-infected subjects compared to uninfected subjects. Antral gastrin amide concentrations were significantly higher in infected subjects. However, the concentrations of the nonamidated gastrin forms (progastrin and glycine-extended gastrin) were significantly lower in the infected subjects, indicating an increased conversion of the precursor forms of gastrin to amidated gastrin, the type known to stimulate gastric acidity. The present study demonstrates that the elevated gastrin concentrations associated with H. pylori infection may be due to a reduction in the paracrine inhibitory effect of SOM on antral gastrin release. In addition, the posttranslational processing of gastrin to the amidated forms is increased in infected subjects, explaining why the elevation in antral gastrin is confined to the amidated form.
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PMID:Expression of progastrin-derived peptides and somatostatin in fundus and antrum of nonulcer dyspepsia subjects with and without Helicobacter pylori infection. 1111 84

There is no general agreement as regards the effect of Helicobacter pylori infection on gastric emptying in patients with functional dyspepsia. Food releases several gastrointestinal hormones, and some of these are known to contribute to the regulation of gastric emptying. The aim of this study was to investigate the influence of H. pylori on gastric emptying in dyspeptic and healthy subjects and to verify whether different hormone secretion patterns are affected by the presence of the bacterium. Twenty-seven patients affected by functional dyspepsia and 30 asymptomatic healthy subjects entered the study. H. pylori presence was assessed in controls by IgG antibodies to H. pylori and [13C] urea breath test, and that in patients by Warthin-Starry stain on gastric biopsies. After ingesting a standard solid-liquid meal, an ultrasound examination of gastric emptying was performed. Plasma concentrations of gastrin, cholecystokinin, and pancreatic polypeptide were measured in the fasting and postprandial period for 4 hours. The incidence of H. pylori infection was not higher in functional dyspepsia patients than in controls. As regards gastric emptying, no difference was detected between patients and controls with and without H. pylori infection. On the contrary, the presence of H. pylori infection determined alterations in gastrin levels, which were higher in controls than in patients. Basal CCK levels were higher in the H. pylori-negative patients than H. pylori-positive patients and controls. In conclusion, H. pylori infection seems not to cause alterations in gastric emptying, but rather alterations in gastrin levels. In contrast, the altered levels of CCK account for its involvement in the pathophysiology of H. pylori-negative dyspepsia.
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PMID:Effect of Helicobacter pylori infection on gastric emptying and gastrointestinal hormones in dyspeptic and healthy subjects. 1127 Jul 93

We present a case with extremely high serum gastrin induced by atrophic gastritis and Helicobacter pylori infection. The patient, a 95-year-old male, was diagnosed with idiopathic chronic diarrhea. During diagnostic work-up, his fasting serum gastrin was up to 2078 pg/mL. The secretin test was negative for gastrinoma. Octreotide scan showed no suspicious lesion except for diffuse faint uptake over the gastric antrum on the 48-hour-delay film. Gastric acidity test revealed achlorhydria. On histology examination, atrophic gastritis with Helicobacter pylori infection was found in the gastric body, but the antral mucus was normal with a slight increase in gastrin-secreting cells. To our knowledge, such extremely high serum gastrin induced by atrophic gastritis and Helicobacter pylori infection has never been reported before.
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PMID:Extreme hypergastrinemia caused by atrophic gastritis and Helicobacter pylori infection--a case report. 1149 Aug 38

Although hypergastrinemia is frequently observed in individuals with a chronic Helicobacter pylori infection, its pathophysiological significance in gastric mucosal inflammation is unclear. The present study was designed to determine if gastrin induces the expression of CXC chemokines in gastric epithelial cells. Human and rat gastric epithelial cells, transfected with gastrin receptor, were stimulated with gastrin. The expression of mRNAs for human interleukin-8 (IL-8) and rat cytokine-induced neutrophil chemoattractant-1 and release of human IL-8 protein were then determined by Northern blot analysis and ELISA, respectively. Gastrin not only induced the expression of mRNAs for these chemokines but also stimulated IL-8 protein release. A luciferase assay using IL-8 promoter genes showed that nuclear factor (NF)-kappaB is absolutely required and activator protein-1 (AP-1) is partly required for the maximum induction of IL-8 by gastrin. An electrophoretic mobility shift assay revealed that gastrin is capable of activating both NF-kappaB and AP-1. In addition, the inhibition of NF-kappaB abrogated gastrin-induced chemokine expression. These results suggest that gastrin is capable of upregulating CXC chemokines in gastric epithelial cells and therefore may contribute to the progression of the inflammatory process in the stomach.
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PMID:Gastrin induces CXC chemokine expression in gastric epithelial cells through activation of NF-kappaB. 1151 86

Helicobacter pylori affects gastric secretion. This functional effect might have a morphometric counterpart. Therefore, the gastric cell secretory compartment was morphometrically assessed in different pathophysiologic conditions related to Helicobacter pylori infection. Nineteen Helicobacter pylori-positive nonduodenal ulcer subjects, 15 omeprazole chronically treated subjects, and 19 duodenal ulcer patients were studied against 19 controls. Somatostatin, gastrin, enterochromaffin-like, and parietal cell density was assessed in gastric biopsies. No differences in any cell type density were found between Helicobacter pylori-positive nonduodenal ulcer subjects and controls. On the contrary, differences were significant when comparing omeprazole and duodenal ulcer patients to controls (higher density of gastrin, enterochromaffin-like, and parietal cells, lower density of somatostatin cells). In duodenal ulcer a reversion to control values followed Helicobacter pylori eradication and ulcer healing. A direct linear correlation between enterochromaffin-like, gastrin, and parietal cell density was demonstrated. An almost complete map of mucosal cells involved in gastric secretion is provided by this study. The cell density pattern, identical to the omeprazole group, points to an impaired feedback control of secretion in duodenal ulcer. The reversion to control values after Helicobacter pylori eradication and ulcer healing demonstrates the pathogenetic role of Helicobacter pylori-host interaction in these changes.
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PMID:Impairment of gastric secretion modulation in duodenal ulcer and in long-term PPI treatment: quantitative morphologic findings and pathophysiologic implications. 1157 48

Helicobacter pylori infection has been found to decrease the expression of antral somatostatin and to increase the release of the acid-stimulating hormone gastrin. The reversal of these changes in gut hormones by the eradication of H. pylori, and in-vivo and in-vitro studies in animals either infected with H. pylori or exposed to H. pylori-related materials may support the somatostatin-gastrin link theory in the pathophysiology of H. pylori infection. The following mechanisms have been proposed to explain the H. pylori infection-associated changes in gut hormones; (1) ammonia produced by H. pylori and monochloramine, (2) effect on somatostatin receptor subtype-2, (3) action of lipopolysaccharide from H. pylori on somatostatin receptor, (4) inflammatory cells and mediators, and (5) bacterial strain diversity. H. pylori infection can alter gastric acid secretion in both directions. The elevated acid secretion in patients with duodenal ulcer is decreased by H. pylori eradication, and is accompanied by the normalization of gut hormones in patients whose H. pylori-induced gastritis is limited to the antrum with hyperacidity. Corpus gastritis and the subsequent development of mucosal atrophy induced by H. pylori result in decreased acid secretion, although the mechanism underlying H. pylori-induced atrophy in some subjects remains unclear. Hypoacidity enhances corpus atrophy and increases gastrin secretion, mediated via a physiological suppression of somatostatin release, features that are also observed in H. pylori infection. Therefore, the capacity of acid secretion and distribution of gastritis or atrophy should be taken into consideration when we discuss the affect of H. pylori on gut hormones.
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PMID:Helicobacter pylori and gut hormones. 1187 70

In Japan, most cases of gastric carcinoid tumor (GCT) are unassociated with either autoimmune gastritis (AIG) showing type-A chronic atrophic gastritis (CAG-A) or Zollinger-Ellison syndrome (ZES). However, the pathogenesis of this tumor remains unknown. Recent studies have determined that Helicobacter pylori infection induces gastric carcinoid in Mongolian gerbils and that H. pylori lipopolysaccharide exerts a mitogenic effect on ECL cells. We examined five patients with histologically diagnosed GCT, 40 patients with H. pylori-positive gastric ulcer (Hp+GU), 24 patients with H. pylori-positive duodenal ulcer (Hp+DU), and 12 patients with AIG showing CAG-A topographically. We compared the prevalence of H. pylori infection, and the levels of gastrin and pepsinogen (PG) in the serum of patients with GCT with those of patients with Hp+GU, or Hp+DU, and AIG. We also investigated the histological characteristics of the tumor and the gastric corpus mucosa in the GCT patients. The levels of serum gastrin and PG I and II were measured using an RIA kit. In all five (100%) patients with GCT, H. pylori infection was present, without any evidence of AIG or ZES. The serum levels of gastrin in the GCT patients were higher than those in either Hp+GU or Hp+DU patients and lower than those in the AIG patients. In contrast, serum PG I levels and the PG I/II ratio were lower in the GCT group than in the Hp+GU or Hp+DU groups. Histologically, all GCTs were ECL cell tumors and peritumoral corporal mucosal atrophy was observed in four of the five patients with GCT. In conclusions, H. pylori infection and hypergastrinemia were found in the patients with GCT without AIG. This finding suggests that H. pylori infection may induce corporal mucosal atrophy and hypergastrinemia that can produce a GCT with time.
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PMID:Gastric carcinoid tumors without autoimmune gastritis in Japan: a relationship with Helicobacter pylori infection. 1191 46

Enterochromaffin-like (ECL) cells are neuroendocrine cells in the gastric mucosa that control acid secretion by releasing histamine as a paracrine stimulant. The antral hormone gastrin and the neural messenger pituitary adenylyl cyclase-activating peptide (PACAP) potently stimulate histamine synthesis, storage, and secretion by ECL cells. Histamine is stored in secretory vesicles via V-type ATPases and vesicular monoamine transporters of subtype 2 (VMAT-2). Plasmalemmal calcium entry occurs via L-type calcium channels upon stimulation with secretagogues. K(+) and Cl(-) channels maintain the membrane potential. Calcium-triggered exocytosis of histamine is mediated by interacting SNARE proteins, especially by synaptobrevin and SNAP-25. Dynamins and amphiphysins appear to play a key role in endocytosis. ECL cells are under transcriptional control of various hormones. Gastrin stimulates transcriptional activity of the histidine decarboxylase (HDC), VMAT-2, and chromogranin A promoter by activation of Sp1 elements and CREB. During chronic Helicobacter pylori infection, pro-inflammatory cytokines are released that can also affect ECL cells, thus impairing their secretory function and viability, which can predispose to hypochlorhydria and gastric carcinogenesis.
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PMID:Physiology of gastric enterochromaffin-like cells. 1222 Nov 95

Gastrin is a hormone produced by G-cells in the normal gastric antrum. However, colorectal carcinoma cells may aberrantly produce gastrin and exhibit increased expression of cholecystokinin B (CCK-B)/gastrin receptors. Gastrin is trophic for the normal gastric oxyntic mucosa and exerts a growth-promoting action on gastrointestinal malignancy. Thus, gastrin may act as an autocrine/paracrine or endocrine factor in the initiation and progression of colorectal carcinoma. The molecular mechanisms involved have not been elucidated. Hypergastrinemia induced by Helicobacter pylori infection is associated with increased cyclooxygenase-2 (COX-2) expression in gastric and colorectal tissues, suggesting the possibility that gastrin up-regulates COX-2 expression in these tissues; this has not been confirmed. We report here that gastrin significantly increases the expression of COX-2 mRNA and protein, the activity of the COX-2 promoter, and the release of prostaglandin E(2) from a rat intestinal epithelial cell line transfected with the CCK-B receptor. These actions were dependent upon the activation of multiple MAPK signal pathways, including ERK5 kinase; transactivation of the epidermal growth factor receptor; and the increased expression and activities of transcription factors ELK-1, activating transcription factor-2, c-Fos, c-Jun, activator protein-1, and myocyte enhancer factor-2. Thus, our findings identify the signaling pathways coupling the CCK-B receptor with up-regulation of COX-2 expression. This effect may contribute to this hormone-dependent gastrointestinal carcinogenesis, especially in the colon.
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PMID:Gastrin stimulates cyclooxygenase-2 expression in intestinal epithelial cells through multiple signaling pathways. Evidence for involvement of ERK5 kinase and transactivation of the epidermal growth factor receptor. 1223 23


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