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)

Numerous GI hormones and peptides, such as gastrin, CCK, secretin, glucagon, somatostatin and EGF, have been shown to stimulate at least part of the trophic response in GI tissues. Whether any of these (or a different one) accounts for gastrointestinal adaptation is unknown. Final proof will entail the demonstration that the endogenous serum levels of one of these increases during the adaptation period to amounts significant to cause the response.
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PMID:Effect of exogenous gut hormones on gastrointestinal mucosal growth. 612 85

In the present study we have investigated the role of human breast-cancer-derived fibroblasts in the proliferation of primary cultures of epithelial cells derived from the same tumor. For this purpose, a co-culture system, using Transwell tissue-culture inserts with microporous membranes was employed. Fibroblasts and epithelial cells were enriched according to differences in their density on Percoll density gradients. The co-culture system was first established using MCF-7 breast cancer cells and a human fibroblast line (HF cells). Insulin, 17 beta-estradiol, EGF and HF cells all significantly stimulated the growth of MCF-7 breast cancer cells. The stimulatory effects of insulin, E2 and EGF were additive to the stimulatory effect of HF cells. These data suggest that (unique) factor(s), other than the above-mentioned growth-promoting compounds, are responsible for the growth-promoting effects of fibroblasts. In half of the human breast cancers investigated, tumor-derived fibroblasts stimulated tumor-derived epithelial cell proliferation. EGF significantly stimulated epithelial cell proliferation in 4 out of 6 cultures. The stimulatory effects of fibroblasts and EGF were additive or synergistic, and were observed in the additional presence of FCS, again suggesting production of unique factor(s) by the fibroblasts. In one culture the fibroblasts significantly inhibited epithelial tumor-cell proliferation. Conversely, the epithelial cells significantly stimulated proliferation of fibroblasts in 3 out of 3 cultures. The somatostatin analogue octreotide significantly inhibited epithelial cell proliferation by 46% in one tumor-cell culture in the absence, but not in the presence, of fibroblasts. In one culture, octreotide significantly inhibited the proliferation of fibroblasts co-cultured with epithelial cells.
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PMID:Role of tumor-derived fibroblasts in the growth of primary cultures of human breast-cancer cells: effects of epidermal growth factor and the somatostatin analogue octreotide. 752 13

This study was undertaken in order to establish the presence of pluripotential neuroblasts in the developing chick CNS. This has been suggested by our previous observations that expression of emerging neuronal phenotypes in the chick embryo CNS is affected by exposure to neurotrophic substances (i.e., GHRH, SRIF, NGF, EGF, muscle-derived factors) or neurotoxins such as ethanol. We have proposed that one mechanism whereby these substances elicit their effects is by shifting phenotypic expression in populations of pluripotential neuroblasts. In order to establish the presence of significant populations of pluripotential neuroblasts, cultures obtained from 3-day-old whole chick embryos (E3WE) were double-stained with antibodies to markers specific for four neuronal phenotypes in various permutations. Cultures at 6 DIV were tested for the presence of tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), gamma-aminobutyric acid (GABA), and somatostatin (SRIF) alone, and in various combinations. We observed a colocalization of all phenotypic markers within neuronal perikarya and processes in more than fifty percent of neuronal cells in these cultures. These data suggest that developing neuroblasts at this stage of embryogenesis possess the machinery necessary to adopt multiple neuronal phenotypes. The colocalization of neurotransmitter proteins in early neuroblasts (60 hr of embryogenesis) supports the recent concept that these substances themselves may influence phenotypic expression and also supports our idea that microenvironmental factors (i.e., ethanol, growth factors) provide signals which affect emerging phenotypes.
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PMID:Early neuroblasts are pluripotential: colocalization of neurotransmitters and neuropeptides. 756 50

Sixty-four kinds of cell lines were examined as to their ability to degrade glucagon using conditioned-media obtained from their protein-free cultures. Two human tumor cell lines were shown to produce this activity, and the cell line, HPC-YO, established from a human pancreatic carcinoma was shown to produce the highest level of activity. The glucagon-degrading enzyme (GDE) was purified from HPC-YO conditioned-medium by a combination of ion-exchange, gel filtration, and hydroxylapatite column chromatographies. The purified GDE also degraded vasoactive intestinal polypeptide (VIP) and secretin, however, it did not cleave EGF, gastrin, insulin, somatostatin, substance P, neurotensin, or growth hormone. The molecular weight of GDE is 83,000, as determined on SDS-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of GDE was blocked, and the five partial amino acid sequences obtained on lysyl-endopeptidase digestion were determined to be N-L-T-E-E-Y-D-V-S-D-G-E-I-E-L-L-Y-E-K, V-E-T-Y-Y-D-L-L-F-E-K, L-Y-W-F-L-D-E-A-K, S-N-S-T-S-Y-V-K, and Y-Y-A-S-T-S-Y-D-D-T-Y-K. The same or homologous amino acid sequences have not been found in known proteins, demonstrating that GDE is a novel peptidase that degrades the secretin family: glucagon, VIP, and secretin.
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PMID:A novel proteinase, glucagon-degrading enzyme, secreted by a human pancreatic cancer cell line, HPC-YO. 777 1

Somatostatin modulates gastrointestinal mucosal growth and differentiation indirectly via inhibition of bioactive peptides and directly by less well understood mechanisms. We studied the direct effects of the somatostatin analog octreotide on proliferation, brush-border enzyme activity, cell-matrix interactions and intracellular cAMP in Caco-2 human intestinal epithelial cells. Proliferation was assessed by cell counting and [3H]thymidine uptake. The brush-border enzymes alkaline phosphatase (AP) and dipeptidyl dipeptidase (DP) were quantitated by synthetic substrate digestion. Adhesion and migration on purified matrix proteins were also measured. Octreotide (10(-9)-10(-5)M) shortened doubling time (46.5 +/- 6.2% at 10(-5) M, n = 20, P < 0.0001) and stimulated [3H]thymidine uptake. Octreotide decreased intracellular cAMP by 19.4 +/- 5.0% (n = 7, P < 0.0001) while dibutyryl-cAMP (10(-6) M) prolonged doubling time by 10.1 +/- 1.5% (n = 8, P < 0.0001), and blocked the octreotide effect. Octreotide decreased AP and DP with maximal effect at 10(-6) M (36.8 +/- 8.3% and 20.5 +/- 9.1%, n > 7, P < 0.0005 respectively). However, mitomycin proliferative blockade prevented octreotide inhibition of AP and DP, suggesting that the mitogenic effects of octreotide had simply decreased average maturity of the cells. Octreotide did not alter Caco-2 adhesion, EGF-or matrix-modulated motility, or integrin surface expression. Octreotide appears to directly stimulate Caco-2 proliferation by decreasing cAMP. These proliferative effects modulate Caco-2 differentiation but do not affect cell-matrix interactions.
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PMID:Octreotide differentially modulates human Caco-2 intestinal epithelial cell proliferation and differentiation by decreasing intracellular cAMP. 870 Oct 39

Changes in endocrine and secretory functions and in the morfology of gastric mucosa in the course of quadruple H. pylori eradication regimen in 50 H. pylori positive patients: 25 with duodenal ulcer (DU) and 25 with non ulcer dyspepsia (NUD) were studied and compared to 10 healthy controls. Therapy resulted in ulcer healing in all DU patients and in 92% eradication of H. pylori in both groups of patients-DU and NUD. In DU and NUD patients in the course of eradication significant decrease in plasma gastrin was observed. Somatostatin concentration in gastric juice increased significantly in DU patients after anti-H. pylori therapy. EGF in gastric content of DU and NUD patients has risen statistically significantly in the course of H. pylori eradication. Gastric acid output and volume flow decreased insignificantly in both groups. The elimination of H. pylori from gastric mucosa in both DU and NUD patients led to significant decrease in the density and activity of gastritis.
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PMID:Hormonal, secretory and morphological alterations in gastric mucosa in the course of Helicobacter pylori eradication in patients with duodenal ulcer and non-ulcer dyspepsia. 928 34

We designed this study to follow exocrine, endocrine and microstructural changes in duodenal ulcer patients with H. pylori infection in the course and after quadruple eradication regimen. Quadruple therapy appeared to be highly effective method of both ulcer healing and H. pylori eradication. We observed enhanced regeneration of gastric mucosa in the course of treatment. Almost immediate decrease of plasma gastrin and increase of plasma somatostatin and EGF concentration in gastric juice were noticed.
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PMID:[Hormonal changes and secretion and stomach mucosal microstructure in the course of H. pylori in patients with duodenal ulcer]. 942

Microstructural, endo- and exocrine changes in gastric mucosa of Non-Ulcer Dyspepsia patients with H. pylori infection in the course of eradication has been studied. Before, during and after anti H. pylori therapy plasma gastrin and somatostatin levels, EGF and somatostatin concentration in gastric juice and basal and pentagastrin stimulated gastric acid secretion were measured. Moreover microstructure of gastric mucosa specimens has been studied. Maximal Acid Output initially higher in NUD patients than in healthy volunteers increased slightly in the course of eradication. Plasma gastrin decreased while EGF and somatostatin concentration in gastric juice increased. After treatment the ratio of patients with pronounced features (activity) of gastritis was significantly reduced.
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PMID:[Endocrine and exocrine gastric mucosal secretion in the course of H. pylori eradication in patients with non-ulcer dyspepsia]. 942 1

Somatostatin and its receptors are widely distributed in the central nervous system and peripheral tissues including those of the gastrointestinal tract (GI tract). The expression patterns of the five known SSTR genes have been analysed in detail by reverse transcription polymerase chain reaction amplifications and in situ hybridizations using tissues dissected from different parts of rat stomach and gut. While SSTR1 mRNA is present at relatively high amounts throughout the gastrointestinal tract, the levels of SSTR2, 3 and 4 mRNAs vary in different regions and SSTR5 mRNA has not been detected. In situ hybridizations revealed the presence of SSTR3 mRNA in enterocytes and in neurons of the myenteric and submucous plexus. These findings are consistent with a role of SSTR3 in the observed somatostatin-mediated inhibition of acetylcholine release from myenteric neurons and of secretomotor neuron activity in the submucous plexus. Sequence analyses of the SSTR1 gene promoter revealed the absence of the canonical TATA and CAAT motifs and the presence of a variety of potential binding sites for transcriptional regulators. Among these are binding sites for GCF, AP-2, AP-4, response elements for somatostatin (SOM-RE), epidermal growth factor (EGF-RE) and cytocines (GAS and NFIL) as well as for tissue-specific factors such as Pit-1 (pituitary) and IDX-1 (pancreatic cells). Mobility shift assays have confirmed that nuclear proteins of pancreatic RIN1046-38 and pituitary GH3 tumour cells bind to oligonucleotides containing the overlapping Pit-1 and IDX-1 binding sites. Thus, the Pit-1/IDX-1 sites may be critical for the activation of the SSTR1 gene in these cell-types.
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PMID:Localization of somatostatin receptor subtype mRNA in the rat gastrointestinal tract and regulation of SSTR1 gene expression. 955 32

Somatostatin exerts its actions through interaction with specific heptahelical G-protein coupled plasma membrane receptors. Five different somatostatin receptor subtypes have been cloned in man. Different receptor subtypes are coupled to different intracellular transmission cascades in a cell type-dependent manner. In general, somatostatin affects cell proliferation either directly: reducing mitogen-activated protein kinase cascade, activating phosphoproteinphosphatase, stimulating EGF-receptors and adenylate cyclase activity; or indirectly reducing the release of autocrine- and/or paracrine-acting growth factors. Somatostatin can exert cytotoxic (G1 phase cell arrest) or cytostatic (apoptosis induction) effects, also depending on the receptor subtype expressed on the target cell. In gastroenteropancreatic neuroendocrine tumours predominance of sst1 and sst2 with a lesser extent of sst3 and sst5 subtype receptors have been demonstrated using sensitive methods. Synthetic analogues with specific decreasing affinity for sst2 > sst5 > sst3 receptor subtypes have been used as antiproliferative drug in the treatment of gastroenteropancreatic tumours. These compounds (octreotide, lanreotide) resulted in a modest growth-inhibition activity either in functioning or in non-functioning tumours. Combination of somatostatin analogues with alpha-interferon produced a more pronounced antiproliferative effect overcoming therapy resistance developed to either single drug. Finally, the development of radio-labelled somatostatin analogue scintigraphy has contributed to gastroenteropancreatic-tumours lesion localization and future more detailed knowledge of somatostatin receptor mechanisms could improve both the diagnostic and therapeutic application of somatostatin analogues.
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PMID:Therapeutic and diagnostic implications of the somatostatin system in gastroenteropancreatic neuroendocrine tumour disease. 1060 18


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