Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Historically, the interplay between basic research and clinical observation has been essential in the development of new therapies for peptic ulcer disease. That histamine is an important regulator of acid secretion emerged from basic research, followed by the clinical development and use of the H2-receptor antagonists. Basic research contributed again by defining the importance of H+/K(+)-ATPase in acid secretion, resulting in a new class of useful antisecretory agents. Basic studies also gave us prostaglandins (PG) as mucosal protective agents. As 'replacement' therapy, clinicians have found that PG are protective against non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcer (GU). Physiologic studies established that somatostatin is a potent inhibitor of acid secretion, providing the stimulus for clinical studies in Zollinger-Ellison (ZE) Syndrome with a synthetic analog (octreotide). Work on isoforms of the parietal cell gastrin receptor has shown differences in the cytoplasmic domain for G protein coupling. This will aid in understanding how receptor changes and coupling to second messengers relate to the aetiopathogenesis of abnormal gastric secretion. Immune cells express mRNA for histamine, muscarinic and gastrin receptors, supporting the relevance of mucosal immunology in gastroenterology, especially in light of Helicobacter pylori-associated gastritis and ulcers. Lab research has revealed a potential role for basic fibroblast growth factor (bFGF), and another endogenous peptide BPC-15, in ulcer healing. The former substance may be responsible for the antiulcer efficacy of sucralfate. Intensive basic work on how H. pylori organisms attach to gastric cells and initiate inflammatory reactions in the mucosa will have unquestionable impact on improved therapy for peptic ulcer disease.
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PMID:Clinical relevance of basic research in peptic ulcer disease. 788 Oct 29

It is unclear why Helicobacter pylori produces different diseases in different persons. High and low acid secretion rates probably contribute to duodenal ulceration and gastric carcinogenesis, respectively. Both of these changes seem to be corrected by eradicating Helicobacter pylori. We are therefore exploring the basic mechanisms and asking why patients react differently? Helicobacter pylori products and certain cytokines released in Helicobacter pylori gastritis release gastrin from G-cells but inhibit parietal cells. Also tumour necrosis factor alpha inhibits somatostatin-cells and interleukin 1 beta inhibits enterochromaffin-like cells. The net result is that antral gastritis tends to increase, whilst corpus gastritis tends to decrease acid secretion. Corpus atrophy further lowers acid through loss of parietal cells. Factors postulated to increase corpus gastritis include host genetics, early acquisition of Helicobacter pylori, more aggressive strains, poor general health and diets high in salt or lacking in antioxidant vitamins. Further research should address the interaction of bacterium, host and environment with a view to preventing the serious clinical outcomes.
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PMID:Host mechanisms: are they the key to the various clinical outcomes of Helicobacter pylori infection? 947 95

Hospitalization for nonvariceal upper gastrointestinal hemorrhage (UGIH) is still common with an incidence of 100/100,000 adults/year. Mortality rates range between 8 and 14%. The most common etiologies of acute UGIH are gastric and duodenal ulcers which are associated with older age, Helicobacter pylori gastritis and nonsteroidal anti-inflammatory drugs. Approximately 70% of UGIH stop spontaneously, 10% bleed continuously and about 20% rebleed in the first 24-72 h. Mortality and the probability of rebleeding have been related to the ulcers' stigmata (Forrest) and to a variety of clinical findings (hematemesis, low initial hemoglobin, signs of shock, coagulopathy and liver disease). It is well established that only patients with continued bleeding or with a risk of rebleeding benefit from endoscopic or medical treatment. Endoscopic treatment (including heater probe, bipolar electrocoagulation, laser and injection therapy) control active bleeding in up to 90% and reduce significantly the rates of further bleeding, the need for blood transfusions, hospital costs and emergency surgery. Medical treatment is still controversial although positive results for somatostatin and octreotide have been found. A meta-analysis including 1,829 patients from 14 randomized trials showed the relative risk for continued bleeding or rebleeding of 0.53 (95% CI, 0.43-0.63) in favor of somatostatin and octreotide. Interventional endoscopy is the first line of treatment for UGIH. Somatostatin and its analogue octreotide may be a useful adjunct to endoscopic management or alternative when endoscopy is unsuccessful, contraindicated or unavailable.
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PMID:Treatment of acute nonvariceal upper gastrointestinal hemorrhage. 1020 31

The conventional view of gastric acid secretion is that a negative feedback mechanism arises in response to high acidity, such that somatostatin keeps G-cells and parietal cells from producing more gastrin and acid, respectively. When the stomach becomes infected, for example with Helicobacter pylori (H. pylori), the feedback mechanism is impaired. In animal models, our laboratory has demonstrated that other types of bacteria besides H. pylori can cause gastritis. For example, under conditions of low acidity, gastritis is secondary to bacterial overgrowth, not production of excessive acid, thus suggesting a new paradigm for the regulation of gastric acid secretion under inflammatory conditions. Cytokines, released during the gastric inflammatory response, including IFN gamma, TNF alpha and IL-1 beta stimulate the G-cell to produce gastrin. Gastrin in turn triggers the release of acid, and hypergastrinemia suppresses somatostatin, the inhibitor of acid. The overall response results in maximal gastric acid output that acts as the stomach's most important anti-microbial agent. The increased acid secretion by the stomach in the presence of H. pylori seems to be part of the innate immune response, in that gastrin and somatostatin are reciprocally regulated by Th1 or Th2 cytokines, respectively. In a mouse model, we showed that octreotide, a somatostatin, analog, is an efficacious treatment for Helicobacter gastritis. In humans, octreotide might accelerate recovery from H. pylori infection, reducing the duration of antibiotic therapy.
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PMID:Modulating the cytokine response to treat Helicobacter gastritis. 1565 28

Somatostatin is a regulatory peptide found in abundance in the stomach. We have previously shown that somatostatin is required for IL-4-mediated resolution of Helicobacter pylori gastritis. In the current study, we hypothesize that somatostatin acts directly on antigen-presenting cells in the stomach to lessen the severity of gastritis. To test this hypothesis, we first show that CD11c+ dendritic cells are present in the infected tissue of mice with H. pylori-induced gastritis. Pretreatment of bone marrow-derived dendritic cells with somatostatin results in decreased IL-12 production, and lower splenocyte proliferation induced by H. pylori-stimulated dendritic cells. Furthermore, octreotide, a somatostatin analogue, is more potent than somatostatin in suppressing IL-12 release by H. pylori-stimulated dendritic cells through an NF-kappaB-independent pathway. In addition, IL-4 stimulates somatostatin secretion from dendritic cells. In conclusion, somatostatin inhibits dendritic cell activation by H. pylori; a possible mechanism by which IL-4 mediates resolution of gastritis. We suggest that octreotide may be effective in treating immune-mediated diseases of the stomach.
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PMID:Somatostatin inhibits dendritic cell responsiveness to Helicobacter pylori. 1637 83