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)

We previously established pluripotent transformed rat islet cell lines, MSL-cells, of which certain clones have been used to study processes of islet beta-cell maturation, including the transcriptional activation of the insulin gene induced by in vivo passage. Thus, successive sc transplantation in NEDH rats resulted in stable hypoglycemic insulinoma tumor lines, such as MSL-G2-IN. Occasionally, hypoglycemia as well as severe weight loss were observed in the early tumor passages of MSL-G and the subclone, NHI-5B, which carry the transfected neomycin and human insulin genes as unique clonal markers. By selective transplantation, it was possible to segregate stable anorectic normoglycemic tumor lines, MSL-G-AN and NHI-5B-AN, from both clones. These tumors cause an abrupt onset of anorexia when they reach a size of 400-500 mg (< 0.3% of total body weight), and the observed weight loss parallels that of starved rats until death results from cachexia. After tumor resection, animals immediately resume normal feeding behavior. Comparative studies of hormone release and mRNA content in anorectic lines, MSL-G-AN and NHI-5B-AN, vs. those in the insulinoma line, MSL-G2-IN, revealed selective glucagon gene expression in both of the anorectic tumors, whereas insulin and islet amyloid polypeptide gene expression were confined to the insulinoma. Both tumor phenotypes produced cholecystokinin and gastrin in variable small amounts, making it unlikely that these hormones contribute to the anorectic phenotype. Tumor necrosis factor (cachectin) was not produced by any of the tumors. Proglucagon was processed as in the fetal islet to products representative of both pancreatic alpha-cell and intestinal L-cell phenotypes, with glucagon and Glp-1 (7-36)amide as the major extractable products. In contrast to the administration of cholecystokinin, neither glucagon, Glp-1 (7-36)amide, nor their combination, affected feeding behavior in fasted mice, suggesting the presence of a hitherto unidentified anorectic substance released from the glucagonoma. We conclude 1) that glucagonomas and insulinomas can be derived from a common clonal origin of pluripotent MSL cells, thus supporting the existence of a cell lineage relationship between islet alpha- and beta-cell during ontogeny; and 2) that our glucagonomas release an anorexigenic substance(s) of unknown nature that causes a severe weight loss comparable to that reported in animals carrying tumor necrosis factor-producing experimental tumors.
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PMID:The dissociation of tumor-induced weight loss from hypoglycemia in a transplantable pluripotent rat islet tumor results in the segregation of stable alpha- and beta-cell tumor phenotypes. 840 49

Patients with Helicobacter pylori-associated gastritis have an increased release of gastrin. The mechanisms by which H. pylori affects the endocrine cells are unclear. We have used primary cultures containing canine antral G cells to examine the effects of human blood mononuclear cells, purified monocytes and lymphocytes, recombinant cytokines, and NH4Cl on gastrin release. Mononuclear cells and purified monocytes in direct contact with G cells stimulated gastrin release dose dependently. Separating mononuclear cells from G cells by Transwell filters with 0.4-micron pore size still produced a significant increase of gastrin release. Three human recombinant cytokines, interferon-gamma, tumor necrosis factor-alpha, and interleukin-2, but not interleukin-6 and interleukin-1 beta, each produced dose-dependent increases of gastrin stimulation. NH4Cl did not stimulate gastrin release. We conclude that mononuclear cells and purified monocytes prepared from human blood, as well as several cytokines, stimulate gastrin release from antral G cells. These factors may play an important role in the pathogenesis of H. pylori-associated hypergastrinemia.
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PMID:Mononuclear cells and cytokines stimulate gastrin release from canine antral cells in primary culture. 896 89

Gastrin gene expression is regulated by developmental cues, pH, and inflammation. These processes are mediated by various extracellular ligands, e.g., growth factors, cytokines, and neuropeptides that also stimulate c-fos gene expression. Therefore, to determine whether Fos is required for stimulation of the gastrin promoter, a c-fos sense expression vector was coexpressed with a gastrin reporter construct in a GH4 rat pituitary cell line. We found that epidermal growth factor (EGF) and tumor necrosis factor-alpha (TNF-alpha) transiently stimulate an increase in Fos protein that precedes stimulation of the gastrin promoter. However, the induction mediated by TNF-alpha was weaker than that mediated by EGF, indicating minimal overlap of the signaling pathways activated by EGF and TNF-alpha. Accordingly, overexpression of c-fos mRNA facilitated primarily EGF rather than TNF-alpha induction of the gastrin promoter. Expression of the c-fos gene in the absence of ligand did not stimulate the gastrin promoter. Thus c-fos gene expression is required but is not sufficient for induction of the gastrin promoter by EGF.
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PMID:Fos is required for EGF stimulation of the gastrin promoter. 899 37

The ECL cells control parietal cells by releasing histamine in their immediate vicinity. Gastrin and pituitary adenylate cyclase-activating peptide (PACAP) stimulate histamine secretion from isolated ECL cells, while somatostatin and galanin inhibit stimulated secretion. Prostaglandin E2 and related prostaglandins likewise suppress ECL-cell histamine secretion. Conceivably, that is how they inhibit acid secretion. In the present study, we examined if prostaglandin E2 can be generated by isolated ECL cells. Rat stomach ECL cells were purified (>90% purity) by counterflow elutriation and gradient centrifugation and cultured for 48 h. ECL cell stimulants (gastrin and PACAP) and inflammatory agents (interleukin-1 beta, tumor necrosis factor-alpha and bradykinin) were tested for their ability to induce prostaglandin E2 accumulation (24-h incubation), measured by radioimmunoassay. Gastrin and PACAP did not affect prostaglandin E2 accumulation but interleukin-1 beta (300 pg/ml), tumor necrosis factor-alpha (10 ng/ml) and bradykinin (1 microM) induced a 2- to 3-fold increase in the amount of prostaglandin E2 accumulated. While the combination of interleukin-1 beta and bradykinin induced a 9-fold increase, the combination interleukin-1 beta+tumor necrosis factor-alpha and bradykinin + tumor necrosis factor-alpha induced additive effects only. The combination of interleukin-1 beta + tumor necrosis factor-alpha + bradykinin did not induce a greater effect than interleukin-1 beta + bradykinin. The effect of interleukin-1 beta + bradykinin was abolished by adding 10 nM hydrocortisone (suppressing phospholipase A2 and cyclooxygenase) or 1 microM indomethacin (inhibiting cyclooxygenase). Incubating ECL cells in the presence of interleukin-1 beta+bradykinin for 24 h reduced their ability to secrete histamine in response to gastrin. The inhibitory effect was reversed by 1 microM indomethacin. Also, increasing the concentrations of hydrocortisone in the medium resulted in an enhanced gastrin-stimulated histamine secretion. Hence, the previously described acid-inhibiting effect of inflammatory agents may be explained by inhibition of ECL-cell histamine mobilization, consequent to enhanced formation of prostaglandin E2 by cells in the oxyntic mucosa, including the ECL cells themselves.
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PMID:Isolated rat stomach ECL cells generate prostaglandin E(2) in response to interleukin-1 beta, tumor necrosis factor-alpha and bradykinin. 1129 Mar 77

Helicobacter pylori and proinflammatory cytokines have a direct stimulatory effect on gastrin release from isolated G cells, but little is known about the mechanism by which these factors regulate gastrin gene expression. We explored whether tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 directly regulate gastrin gene expression and, if so, by what mechanism. TNF-alpha and IL-1 significantly increased gastrin mRNA in canine G cells to 181 +/- 18% and 187 +/- 28% of control, respectively, after 24 h of treatment. TNF-alpha and IL-1 stimulated gastrin promoter activity to a maximal level of 285 +/- 12% and 415 +/- 26% of control. PD-98059 (a mitogen-activated protein kinase kinase inhibitor), SB-202190 (a p38 kinase inhibitor), and GF-109203 (a protein kinase C inhibitor) inhibited the stimulatory action of both cytokines on the gastrin promoter. In conclusion, both cytokines can directly regulate gastrin gene expression via a mitogen-activated protein kinase- and protein kinase C-dependent mechanism. These data suggest that TNF-alpha and IL-1 may play a direct role in Helicobacter pylori-induced hypergastrinemia.
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PMID:TNF-alpha and interleukin 1 activate gastrin gene expression via MAPK- and PKC-dependent mechanisms. 1170 45

H. pylori colonisation of the stomach causes the recruitment of the inflammatory cells by the adherence of the bacteria with the epithelium and the release of factors of virulence either to the contact (oipA or other soluble factors) or in the cell by translocation (CagA). Such contact triggers interleukin 8 expression in the epithelial cell and attracts lymphocytes and monocytes into the chorion. Bacterial lipopolysaccharide and urease support the activation of these inflammatory cells. The lymphocytes produce pro-inflammatory cytokines, which direct the immune response towards the Th1 pathway. The variability of the inflammatory response depends on hereditary factors of the host such as the interleukin 1 genotypes, which determine the level of the pro-inflammatory cytokine expression, and of bacterial factors such as the cag pathogenicity island, the lipopolysaccharide and the vacuolating toxin, vacA. The mucosal inflammation provokes apoptosis and atrophy of the epithelial cells through the effect of pro-inflammatory cytokines and free radicals. Epithelial proliferation is a consequence of excessive apoptosis caused by the infection. It is stimulated by the expression of inducible cyclo-oxygenase and inducible nitric oxide synthase. The development of atrophic gastritis towards cancer is supported by nitric oxide which has a mutagenic effect on DNA and inhibits p53 protein and by the bacterium itself which decreases DNA mismatch repairing activity. The gastritis induced by Helicobacter pylori changes acid secretion according to the prevalent location of the gastritis in the antrum or in the gastric body. Prevalent gastritis in the gastric body causes hypochlorhydria by reducing the release of histamin from ECL cells and inhibiting the parietal cells through the effect of tumor necrosis factor and interleukin 1-beta. Hypochlorhydria is more marked among patients having a pro-inflammatory genotype for interleukin 1-beta and those infected by bacteria with virulence factors. In the event of antrum predominant gastritis, the pro-inflammatory cytokines cause a reduction of somatostatin and gastrin releases from the D and the G cells, respectively. The result of all is increased maximal acid output and the meal-stimulated acid secretion.
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PMID:[What are the gastric modifications induced by acute and chronic Helicobacter pylori infection?]. 1270 Apr 95

The etiology of functional dyspepsia is not known. The objective of the present study was to determine the characteristics of functional dyspepsia in Western Turkey. We divided 900 patients with functional dyspepsia into three subgroups according to symptoms: ulcer-like (UL), 321 (35.6%), motility disorder-like (ML), 281 (31.2%), and the combination (C) of these symptoms, 298 (33.1%). All patients were submitted to endoscopic evaluation, with two biopsies taken from the cardia and corpus, and four from the antrum of the stomach. All biopsy samples were studied for Helicobacter pylori (Hp) density, chronic inflammation, activity, intestinal metaplasia, atrophy, and the presence of lymphoid aggregates by histological examination. One antral biopsy was used for the rapid urease test. Tissue cagA status was determined by PCR from an antral biopsy specimen by a random sampling method. We also determined the serum levels of tumor necrosis factor-alpha (TNF-alpha) and gastrin by the same method. Data were analyzed statistically by the Kolmogorov-Smirnov test and by analysis of variance. Hp and cagA positivity was significantly higher in the UL subgroup than in the others. The patients in the ML subgroup had the lowest Hp and cagA positivity and Hp density. The ML subgroup also showed the lowest level of Hp-induced inflammation among all subgroups. The serum levels of TNF-alpha and gastrin did not reveal any difference between groups. Our findings show a poor association of Hp with the ML subgroup of functional dyspepsia, but a stronger association with the UL and C subgroups.
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PMID:Functional dyspepsia: relationship between clinical subgroups and Helicobacter pylori status in Western Turkey. 1279 4

Lipopolysaccharide (LPS) is one of the virulence factors in the Helicobacter pylori (Hp)-infected stomach, but it remains unknown whether single and prolonged pretreatment with Hp-LPS can affect the course of gastric damage induced by aspirin (ASA). We compared the effects of Hp-LPS with those induced by LPSs isolated from intestinal Bacteroides fragilis, Yersinia enterocolitica, and Campylobacter jejuni applied for 4 days on acute ASA-induced gastric lesions in rats. The area of ASA-induced gastric lesions, gastric blood flow (GBF), expression of mRNA and protein of leptin and plasma leptin, gastrin, interleukin-1beta, and tumor necrosis factor-alpha levels were examined. Single (once) or repeated (five times) i.p. injections of Hp-LPS (1 mg/kg) or intestinal LPSs failed to produce macroscopic gastric damage and did not affect the GBF when compared with vehicle. Hp-LPS injected repeatedly suppressed the gastric acid secretion, up-regulated leptin mRNA and protein, and increased plasma leptin and gastrin levels. Hp-LPS significantly reduced the ASA-induced gastric damage and the accompanying decline in the GBF, and these effects were significantly attenuated by capsaicin denervation and selective antagonism of cholecystokinin-B (CCK2) receptors by RPR-102681 [N-(metoxy-3 phenyl) N-(N-methyl N-phenyl-carbamylmethyl) carbamoylmethyl]-3 ureido]-3 phenyl]-2 propronique] but not by loxiglumide, an antagonist of CCK1 receptors. We conclude that 1) daily application of Hp-LPS enhances gastric mucosal resistance against ASA damage due to the increase of GBF and the expression and release of leptin and gastrin exerting trophic and gastroprotective effects, and 2) this enhanced resistance to ASA damage in Hp-LPS-adapted stomach is mediated by the sensory afferents and specific CCK2/gastrin receptors.
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PMID:Involvement of capsaicin-sensitive afferent nerves and cholecystokinin 2/gastrin receptors in gastroprotection and adaptation of gastric mucosa to Helicobacter pylori-lipopolysaccharide. 1502 38

The present study investigated the effect of the soybean polyphenol genistein on the stomach using a water immersion restraint (WIR) stress model. Male Wistar rats were administered 50 or 100 mg/kg/d of genistein for 2 wk or were not given any drug. Rats were subjected to WIR stress for 4 h. At the end of the WIR period, rats were sacrificed. Subsequently, rats underwent measurement of the ratio of the mucosal hemorrhagic erosion area to the whole stomach body area, myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, thiobarbituric acid reactive substances (TBARS) level, and proinflammatory cytokines (tumor necrosis factor (TNF)-a and cytokine-induced neutrophil chemoattractant (CINC)-1) levels in the gastric tissue. Furthermore, an isolated rat stomach infusion model was employed for the endocrinological investigation of the effect of genistein. The extracted stomach canal and the vascular system, which comprised the experimental model, were subjected to perfusion. After 20 min of perfusion, the perfusate from the portal vein was collected, and the concentrations of histamine, gastrin, and somatostatin in the perfusate were measured. Experiments demonstrated that genistein administration resulted in significant suppression of WIR stress-induced gastric mucosal injury and MPO activity, Further, genistein significantly elevated SOD activity and significantly suppressed the TBARS level, production of TNF-alpha and CINC-1, and secretion of gastrin, histamine, and somatostatin. These data suggest that genistein protected against gastric mucosal injury, likely via its ability to inhibit oxidation, inflammation, and secretion of gastrin and histamine.
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PMID:The protective effect of the soybean polyphenol genistein against stress-induced gastric mucosal lesions in rats, and its hormonal mechanisms. 1708 54

Helicobacter pylori (H. pylori) infection causes chronic gastritis and is also related to gastric carcinoma. The present study focused on severity of H. pylori-induced gastritis as a determinant of carcinogenesis. Seven-week-old male Mongolian gerbils were inoculated with H. pylori at experimental weeks 0, 12, or 18, then given N-methyl-N-nitorosourea (MNU) from weeks 20-40. At week 70, stomachs were then excised for histological examination 70, 58, or 52 weeks after H. pylori inoculation, respectively (Groups A, B, and C for long-, middle-, and short-term). The respective incidences of glandular stomach adenocarcinomas were 65.0% (13/20), 20.0% (2/10), and 23.0% (3/13) (P<0.05). Higher scores of infiltration of inflammatory cells, hyperplasia, intestinal metaplasia and mucosal bromodeoxyuridine (BrdU) labeling index in antrum and corpus mucosa, were seen in group A than B or C (P<0.05) and serum anti-H. pylori IgG titer and gastrin levels were also significantly higher, along with mRNA levels for mucosal interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). The results demonstrated the term and severity of H. pylori infection to play important roles in gastric carcinogenesis, with essential involvement of chronic inflammation, especially increased rates of cell proliferation, in H. pylori-associated carcinogenesis.
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PMID:Severity of gastritis determines glandular stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbils. 1728 48


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