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)

A soluble somatostatin-binding protein was detected in the cytosol fractions of various rat, human and bovine tissues. Maximum binding occurred at pH8.0-8.5 and was Ca(2+)-dependent. The specific binding of somatostatin per 10mug of cytosol protein from 12 rat tissues ranged between 36 and 15%, and 3% for peripheral blood cells. There was also substantial binding in cytosol from human anterior pituitary and liver, and bovine anterior pituitary. The specific binding in rat and human plasma in the presence of EDTA was only 1%. Gel filtration suggested a molecular weight of approx. 80000 for the somatostatin-binding protein from several sources. Exposure of the binding protein to trypsin eliminates somatostatin-binding activity but ribonuclease and deoxyribonuclease have no effect. The binding protein is thermolabile, ethanol-precipitable, and not completely specific for somatostatin. Bound (125)I-labelled [Tyr(1)]somatostatin is not easily displaced by excess of unlabelled somatostatin. The effects of dithiothreitol and mercaptoethanol on the binding of (125)I-labelled [Tyr(1)]somatostatin to the binding protein suggests that binding involves two sequential steps, first loose binding, then disulphide linkage. Since semipurified somatostatin-binding protein causes a dose-related inhibition of the binding of (125)I-labelled [Tyr(1)]somatostatin in radioimmunoassays for somatostatin, estimates of somatostatin content of tissue extracts by radioimmunoassay in some cases may be spuriously high. It is not yet clear whether the binding protein is a true cytosol protein or an easily solubilized membrane protein.
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PMID:Properties of soluble somatostatin-binding protein. 2 54

Extracts of mouse hypothalamus made in acid/urea containing protease inhibitors were analyzed for somatostatin immunoreactivity after molecular sieve filtration on Sephadex G-50. Higher molecular weight (higher-M(r)) somatostatin-like forms with apparent molecular weights of 15,000, 10,000, and 6000 could be identified, besides the molecular weight 1600 somatostatin. Immunological identities with somatostatin were unambiguously demonstrated by the analysis of the displacement curves in the radioimmunoassay. The M(r) 15,000, 6000, and 1600 species were purified by affinity chromatography on an anti-somatostatin immune serum covalent conjugate with Sepharose used as immunoadsorbant. After disulfide reduction by dithiothreitol, the size of the M(r) 15,000 and 6000 somatostatin-like species was assessed either by molecular sieve filtration or by polyacrylamide gel electrophoresis. The results indicated that the higher-M(r) somatostatin-like species isolated from the hypothalamus did not result from hormone polymerization by means of disulfide interchange. The processing in vitro of the 15,000 higher-M(r) form of somatostatin was achieved by proteolytic enzymes coeluted with this species during the fractionation of hypothalamic extracts. Under neutral pH conditions the intermediary higher-M(r) forms were generated together with the M(r) 1600 somatostatin-like species. This processing activity could be either strongly inhibited at acidic pH or in acid/urea medium or else eliminated by selective immunoadsorption of the 15,000 higher-M(r) form. Neither trypsin nor the gamma subunit of 7S nerve growth factor was able to produce this processing, suggesting that enzymes with other kinds of specificity may be involved. It is concluded that somatostatin biosynthesis in the mouse hypothalamus may occur via a high-M(r) precursor that is processed into intermediary forms leading to the tetradecapeptide hormone.
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PMID:Higher molecular weight forms of immunoreactive somatostatin in mouse hypothalamic extracts: evidence of processing in vitro. 4 8

A human pancreatic beta cell tumor was maintained in monolayer cell culture for 80 days. The culture was terminated because of bacterial infection. Probably because extensive trypsin-collagenase dissociation was unnecessary, the dissociated cells attached much more quickly to the surface of the culture flask than do rat pancreatic cells obtained by enzymatic dissociation. Insulin release not only oscillated widely during the first 40 days of culture but also showed a decline from 380 mU the first week to about 50 mU/week the seventh week. For some unknown reason fibroblast overgrowth was not a major problem. Reduction of the medium glucose concentration from 16.5 mM to 5.5 mM did not alter insulin release rate. At glucose concentration of 16.5 mM, somatostatin 1.0 mug/ml reduced insulin release by 40%. From our previously reported studies on the effect of somatostatin on insulin release by monolayer cell cultures of rat endocrine pancreas, we conclude that the constant release of insulin by the tumor cells is relatively nonstimulated. We have confirmed that monolayer cultures of human pancreatic beta cell tumor do not represent a good model for normal human beta cell function because of the major shortcoming of an apparent inability to recognize glucose as a secretogogue.
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PMID:Monolayer cell culture of human pancreatic beta cell tumor: effect of glucose and somatostatin on insulin release. 17 3

In 4 dogs with chronic duodenal and gastric fistulae, exocrine pancreatic function was assessed by cannulating the pancreatic duct and collecting the duodenal contents. Both methods were applied in each animal. Pancreatic secretion was stimulated by infusion of 2 CHR units of pancreozymin and secretin or by administration of a liquid test meal, injected into the stomach through the gastric fistula. During both experiments 3.5 microgram/kg somatostatin was given as bolus injection followed by an infusion of 3.5 microgram/kg/h. Somatostatin caused a significant reduction in protein and amylase output and in the bicarbonate concentration during stimulation with pancreozymin-secretin. Volume and bicarbonate slightly decreased but not to a significant extent. Duodenal volume and the duodenal activities of trypsin and amylase were significantly reduced during test meal stimulation and somatostatin infusion. Somatostatin is a potent inhibitor of exocrine pancreatic function mainly influencing enzyme secretion.
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PMID:Effect of somatostatin on exocrine pancreatic secretion stimulated by pancreozymin-secretin or by a test meal in the dog. 64 May 82

Intrahepatic bile duct epithelial cells, or cholangiocytes, contribute to bile secretion in response to hormones, including secretin. However, the mechanism by which secretin stimulates ductular bile flow is unknown. Since recent data in nonhepatic epithelia have suggested a role for exocytosis in fluid secretion, we tested the hypothesis that secretin stimulates exocytosis by isolated cholangiocytes. Cholangiocytes were isolated from normal rat liver by a newly described method employing enzymatic digestion and mechanical disruption followed by immunomagnetic separation using specific monoclonal antibodies, and exocytosis was measured using a fluorescence unquenching assay employing acridine orange. Secretin caused a dose-dependent (10(-12)-10(-7) M) increase in acridine orange fluorescence by acridine orange-loaded cholangiocytes with a peak response at 10 min; the half-maximal concentration of secretin was 7 x 10(-9) M. The secretin effect was inhibited by preincubation of cholangiocytes with colchicine (30% inhibition, p less than 0.05) or trypsin (90% inhibition, p less than 0.001); no inhibition was seen with lumicolchicine and heat-inactivated trypsin. Cholecystokinin, insulin, and somatostatin had no effect on fluorescence of acridine orange-loaded cholangiocytes; secretin had no effect on fluorescence of acridine orange-loaded hepatocytes or hepatic endothelial cells. Exposure of isolated cholangiocytes to secretin at doses that stimulated exocytosis caused a dose-dependent increase in cyclic AMP levels (218% maximal increase, p less than 0.05); moreover, an analogue of cyclic AMP stimulated exocytosis by cholangiocytes. Secretin had no effect on intracellular calcium concentration using Fura-2-loaded cholangiocytes assessed by digitized video microscopy. Our results demonstrate, for the first time, that secretin stimulates exocytosis by rat cholangiocytes. The effect is cell- and hormone-specific, dependent on intact microtubules, on a protein(s) on the external surface of cholangiocytes, and on changes in cellular levels of cyclic AMP. The results are consistent with the hypothesis that secretin-induced changes in bile flow may involve an exocytic process.
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PMID:Secretin stimulates exocytosis in isolated bile duct epithelial cells by a cyclic AMP-mediated mechanism. 132

The regulation of acid secretion was clarified by the development of H2-receptor antagonists in the 1970s. It appears that gastrin and acetylcholine exert their effects on acid secretion mainly by stimulation of histamine release from the enterochromaffin-like (ECL) cell of the fundic gastric mucosa. The isolated ECL cell of rat gastric mucosa responds to gastrin/cholecystokinin (CCK), acetylcholine, and epinephrine with histamine release and to somatostatin and R-alpha-methyl histamine by inhibition of histamine release. Histamine and acetylcholine stimulate the parietal cell by elevation of cAMP or [Ca]i by activation of H2 or M3 receptors, respectively. These independent pathways converge to activate the gastric acid pump, the H+,K+ ATPase. Activation is a function of the association of the ATPase with a potassium chloride transport pathway that occurs in the membrane of the secretory canaliculus of the parietal cell. Hence the secretory canaliculus is the site of acid secretion, the acid being pumped into the lumen of the canaliculus. The pump is composed of two subunits, a large catalytic and a smaller glycosylated protein. This final step of acid secretion has become the target of drugs also designed to inhibit acid secretion. The target domain of the benzimidazole class of acid pump inhibitors is the extracytoplasmic domain of the pump that is secreting acid, and the target amino acids are the cysteines present in this domain. The secondary structure of the pump can be analyzed by determining trypsin-sensitive bonds in intact, cytoplasmic-side-out vesicles of the ATPase, and it has been shown that the alpha subunit has at least eight membrane-spanning segments. Omeprazole, the first acid pump inhibitor, forms a disulfide bond with cysteines in the extracytoplasmic loop between the fifth and sixth membrane-spanning segment and to a cysteine in the extracytoplasmic loop between the seventh and eight segments, preventing phosphorylation of the pump by ATP. As a result of the effective and long-lasting inhibition of acid secretion by the acid pump inhibitor, superior clinical results have been found in all forms of acid-related disease.
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PMID:Acid secretion and the H,K ATPase of stomach. 134 Oct 65

Somatostatin 28 (S-28), originating in gastrointestinal cells, is secreted into the circulation and increases in humans after ingestion of a mixed meal. To evaluate the possibility that the increased levels of S-28 post cibum might modulate the release of enzymes and bicarbonate from the exocrine pancreas, S-28 was infused intravenously into healthy volunteers to levels seen after food intake. During S-28 infusion, the output of lipase, trypsin, amylase, and bicarbonate stimulated by either exogenous cholecystokinin octapeptide or endogenous signals from intraduodenal administration of tryptophan or a mixture of amino acids was significantly reduced. It is concluded that S-28 released from the gut during food intake modulates pancreatic exocrine function in humans.
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PMID:Evidence for hormonal inhibition of exocrine pancreatic function by somatostatin 28 in humans. 135 58

Astrocytes were prepared from rats of 4 ages, embryonic day 20, postnatal days 3 and 8, and adult, in order to study the developmental time course of expression of enkephalin and somatostatin (SS). Glial fibrillary acidic protein (GFAP) content was constant in both cortical and cerebellar astrocytes prepared from all ages. SS mRNA and peptide decreased over this developmental time course in cerebellar astrocytes; the time course of changes in SS mRNA paralleled that for rat cerebellum. Proenkephalin (PE) mRNA increased about 3-fold in cerebellar astrocytes from embryonic day 20 to adult but remained constant in cortical astrocytes; in contrast, PE mRNA showed a 10- to 12-fold increase in rat cerebellum and cortex developmentally. For both cerebellar and cortical astrocytes, free met-enkephalin decreased from embryonic day 20 to adult, whereas total met-enkephalin (measured following trypsin-carboxypeptidase B digestion of the extracts) increased. These results suggest (1) that there is a developmental regulation of the expression of both enkephalin and SS peptides in astrocytes, and (2) that the regulation occurs at the level of transcription for SS but at the level of precursor processing for PE. Possible trophic functions for astrocyte-derived peptides early in CNS development are discussed.
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PMID:Developmental expression of the proenkephalin and prosomatostatin genes in cultured cortical and cerebellar astrocytes. 135 15

The new long-acting somatostatin analogue octreotide (SMS 201-995) was investigated for its influence on secretagogue-stimulated human exocrine pancreatic secretion. Eighteen healthy volunteers participated in the study. During duodenal intubation with a background stimulation of either secretin 1 U.kg/h or secretin 1 U.kg/h + ceruletide, 120 ng.kg/h, octreotide was infused at doses of 5, 20 and 80 micrograms/h in a placebo-controlled randomized double-blind crossover trial. Duodenal juice samples were collected in 10-min intervals, and amylase, trypsin, chymotrypsin, and bicarbonate were measured in the individual fractions. During secretin stimulation, amylase was inhibited between 41 and 59%, trypsin between 28 and 72%, chymotrypsin between 55 and 70%, and bicarbonate between 0 and 31% with 5, 20 and 80 micrograms/h octreotide. During secretin and ceruletide stimulation, amylase was significantly inhibited by 84%, 78%, 81%, trypsin by 76%, 55%, 52%, chymotrypsin by 77%, 55%, 60%, and bicarbonate by 25%, 11%, 19% with 5, 20, and 80 micrograms/h octreotide, respectively (all decreases P less than 0.05). The long-acting somatostatin analogue octreotide was confirmed to be a potent inhibitor of stimulated human exocrine pancreatic secretion. The near maximal inhibitory potency of octreotide was achieved at a dose of only 5 micrograms/h. This finding may be of value in the planning of therapeutic studies with octreotide.
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PMID:Inhibition of human exocrine pancreatic secretion by the long-acting somatostatin analogue octreotide (SMS 201-995). 137 38

A phosphoryl protein tyrosine phosphatase (PTPase) activity has been characterized in rat pancreatic acinar membranes using 32P-labeled poly(Glu,Tyr) as substrate. Acinar membranes exhibited a high affinity for the substrate, with an apparent Km of 0.46 microM and an apparent Vmax of 0.9 nmol.mg protein-1.min-1. Acinar membrane PTPase activity displayed specific characteristics of other PTPases; it was inhibited by the inhibitors Zn2+, orthovanadate and by the divalent cations Mn2+ and Mg2+, and was stimulated by the reducing-agent dithiothreitol. It was also inhibited by soybean trypsin inhibitor and stimulated by trypsin. Gel permeation of pancreatic acinar membranes gave a single peak of enzyme activity with an apparent molecular mass of 70 000 Da. Further purification by HPLC on DEAE revealed two peaks of PTPase activity at 120 mM and 180 mM NaCl. These two peaks reacted in a Western-blot procedure with anti-(peptide) serum directed towards conserved domain of PTPase as a common 67-kDa form associated with lower-molecular-mass proteolytic fragments (31-56 kDa). Incubation of pancreatic acini with somatostatin analogues, SMS 201-995 or BIM 23014, resulted in a stimulation of membrane PTPase activity. The stimulation was rapid and transient, with a maximal level reached within 15 min of addition. The two analogs stimulated PTPase activity in a dose-dependent manner with half-maximal activation occurring at 7 pM and 37 pM and maximal activation at 0.1 nM and 0.1-1 nM for SMS 201-995 and BIM 23014, respectively. The stimulated-membrane PTPase activity also eluted at an apparent molecular mass of 70 kDa in gel-permeation chromatography. The two analogs inhibited the binding of [125I-Tyr3]SMS 201-995 to pancreatic acinar membranes with similar relative potencies to that observed on stimulation of PTPase activity. We conclude that pancreatic acinar membranes possess a low-molecular-mass PTPase which is stimulated by somatostatin analogs at concentrations involving activation of membrane somatostatin receptors.
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PMID:Stimulation of a membrane tyrosine phosphatase activity by somatostatin analogues in rat pancreatic acinar cells. 149 47


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