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)

The effect of somatostatin on the course and severity of experimental pancreatitis was tested. Acute pancreatitis was induced in 210 Sprague-Dawley rats by injecting a 4.3% sodium taurocholate solution, saturated with trypsin, into a temporarily closed duodenal loop. Immediately after the end of the surgical procedure somatostatin or, alternatively, normal saline were administered as a bolus followed by continuous subcutaneous infusion for 9 h. Ninety rats (30 untreated, 30 saline-treated and 30 somatostatin-treated) were sacrificed 10 h after the induction of pancreatitis to assess the histologic severity of pancreatic lesions, the amount of peritoneal exudate and the circulating levels of amylase. In another 120 rats (40 untreated, 40 saline-treated and 40 drug-treated) the mortality rate was evaluated so that the histologic examination of the pancreas followed spontaneous death. In sacrificed animals somatostatin treatment lowered serum amylase levels and definitely improved pancreatic histopathology (edema, leucocyte infiltration and necrosis). The drug prevented the occurrence of severe necrosis in all treated animals. Somatostatin did not affect the mortality rate of pancreatitic rats (70%) although post-mortem histologic examination revealed significantly less pancreatic histopathology in drug-treated rats than in their controls.
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PMID:Effects of somatostatin on acute pancreatitis induced in rats by injection of taurocholate and trypsin into a temporarily closed duodenal loop. 290 46

Terbutaline, a selective beta 2-adrenoreceptor agonist, has recently been advocated as a potential agent for treating patients with pancreatic fistulae. In the present study, we attempted to quantify the presumed effects of terbutaline on exocrine pancreatic secretion in humans and to characterize possible mechanisms of action. In six healthy volunteers, the pancreas was stimulated by infusion of graded doses of secretin (15.5-250 ng/kg/h) or by infusion of secretin (15.5 ng/kg/h) plus graded doses of caerulein (3.3-30 ng/kg/h). The experiments were repeated in each subject without and with administration of terbutaline. Pancreatic secretion was assessed by a marker perfusion technique and plasma somatostatin and pancreatic polypeptide (PP) levels by radioimmunoassay. Terbutaline had no significant effect on secretin-stimulated pancreatic secretion, but significantly inhibited caerulein-stimulated pancreatic fluid secretion and trypsin output. Plasma somatostatin and PP levels were not affected by terbutaline. The inhibitory effect required the administration of pharmacologically large doses of terbutaline. We conclude that the weak inhibitory effect of terbutaline on exocrine pancreatic secretion is not mediated via somatostatin nor PP and that our data do not support a major role for beta-adrenergic mechanism as regulator of pancreatic secretion.
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PMID:Mechanisms of terbutaline-induced inhibition of exocrine pancreatic secretion in humans. 290 21

The aim of the present study was to investigate the short-term (8-day) effects of feeding a raw soybean diet on exocrine pancreatic secretion and the plasma levels of gastrointestinal hormones in pigs. After adaptation to a heated soybean diet, 6 pigs (36.5 +/- 0.8 kg) were fitted with permanent fistulae of the pancreatic duct, the duodenum and a carotid artery. After post-surgical recovery of 8 days, the animals were submitted to two experimental periods, a 4-day period during which they were fed the heated soybean diet and an 8-day period during which they received the raw soybean diet. Exocrine pancreatic secretion and plasma levels of secretin, cholecystokinin, VIP, PP, somatostatin and gastrin were monitored each day of the two experimental periods. On the first day of raw soybean ingestion and till its end, the daily volume of pancreatic juice was higher than the mean volume measured during heated soybean ingestion. On the contrary, daily total protein output was unchanged. Specific activities of chymotrypsin, amylase and lipase were not modified by the raw soybean diet whereas, from the third day of the experimental period, that of trypsin was higher than the corresponding mean value determined during the first experimental period. Plasma levels of secretin and VIP were higher throughout raw soybean ingestion than the corresponding mean levels determined during the first experimental period. The plasma level of cholecystokinin increased only slightly and in the first days of the second experimental period only. The other gastrointestinal hormones studied were slightly (gastrin) or not (somatostatin, PP) affected by raw soybean feeding. It is suggested that feedback control of exocrine pancreatic secretion in pigs was the mechanism involved in the increase of pancreatic juice observed when raw soybean was fed. This volume increase would result from secretin release into the blood.
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PMID:Short-term (8-day) effects of a raw soybean diet on exocrine pancreatic secretion and plasma gastrointestinal hormone levels in the pig. 371 92

Solid and papillary epithelial neoplasms of the pancreas from six female patients were studied using immunohistochemistry and electron microscopy to define better their histogenesis. The tumors ranged in diameter from 5 to 15 cm (average: 9 cm), and, on cross section, most had areas of hemorrhage and necrosis, sometimes extensive. Microscopically, there was a solid and pseudopapillary pattern, with tumor cells typically having ovoid nuclei with delicate folding and indistinct nucleoli. Of note were the following: a relatively low mitotic rate (range: 0-6/20 hpf), the presence of hyaline globules (four of six cases), and collections of foam cells (three of six cases). Staining for cytoplasmic argyrophil granules was negative in each case. Ultrastructurally, the solid and papillary epithelial neoplasms of the pancreas showed evidence of acinar or ductular differentiation. Two contained zymogen granules, one had intermediate filaments (probably keratin), and three had abundant rough endoplasmic reticulum and mitochondria. Immunostaining was positive for chymotrypsin (six of six cases), trypsin (four of six), and amylase (three of six). None was positive for alpha-1-antitrypsin, neuron-specific enolase, pancreatic polypeptide, gastrin, glucagon, somatostatin, or insulin. The findings support an origin from exocrine pancreas, and follow-up indicates a low rate of malignancy, with local recurrence in two of the six patients.
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PMID:Solid and papillary epithelial neoplasm of the pancreas. An ultrastructural and immunocytochemical study of six cases. 381 76

Previously, we reported that pancreatic acini have specific receptors for the insulin-like growth factors (IGF) I and II. We now report that the binding of 125I-labeled IGF II to mouse pancreatic acini is maximally increased by 100 nM insulin (51%) and is maximally reduced by 10 nM cholecystokinin octapeptide (CCK8) (34%), but is not affected by other regulatory peptides such as somatostatin or glucagon. Since many polypeptide hormones are internalized, we determined whether this regulation of IGF II binding occurred via a change in internalization. Acid washing or trypsinization has been shown to remove surface-bound hormone while the acid- or trypsin-resistant radioactivity represents internalized radioligand. Insulin increased and CCK8 decreased the internalization of IGF II as determined by these techniques. Studies of IGF II binding to acini at low temperature (15 degrees C) and binding to particulate fractions from acini were also consistent with the effect of insulin to increase and CCK8 to decrease the internalization of IGF II. When insulin and CCK8 were added together, the inhibitory effect of CCK8 predominated, indicating that CCK8 acted distal to the effect of insulin. Several lines of evidence suggest that this effect of CCK8 was via the CCK receptor and was mediated via a change in intracellular Ca2+: the effect of CCK8 on inhibiting IGF II binding was blocked by the cholecystokinin antagonist N2,O2'-dibutyryl cGMP; the cholinergic agent carbachol (1-100 microM), which acts through the muscarinic receptor to increase intracellular Ca2+, also inhibited IGF II binding; the Ca2+ ionophore A23187 (1-5 microM) mimicked the effects of CCK8 and carbachol. These data indicate, therefore, that CCK8 and possibly insulin may regulate the internalization of IGF II via intracellular Ca2+. Moreover, the data raise the possibility that alterations of hormone internalization may be a general phenomenon of hormone-hormone interaction.
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PMID:Effect of intracellular Ca2+ on insulin-like growth factor II. internalization into pancreatic acini. Roles of insulin and cholecystokinin. 609 32

Many small biologicaly active peptides are derived from larger precursor forms which fulfil a variety of roles in the synthesis, segregation and intracellular migration of secretory products. Limited proteolysis may occur at several stages during this process, giving rise to products that are either degraded (e.g. the prepeptides) or discharged coordinately from their cells of origin during exocytosis (e.g. insulin and C-peptide). Molecular defects have recently been found to occur at cleavage sites in proinsulin as well as in other proproteins, and these point mutations may, in some instances, be responsible for familial metabolic disorders. The nature and cell specificity of the proteolytic enzymes involved in the conversion of the various precursor forms remains unresolved. Recent studies in our laboratory have led to the identification of precursors of glucagon and somatostatin in rat islets of Langerhans. Analysis of tryptic maps of these precursors has shown that a trypsin-like enzyme would be sufficient to cleave the C-terminally located somatostatin sequence from its precursor (relative molecular mass 12,500), but that both trypsin-like and carboxypeptidase B-like enzymes would be necessary to cleave the internal glucagon sequence from its prohormone (relative molecular mass 18,000). Molecular cloning techniques have provided valuable new approaches to analysing the structures of a variety of precursor forms, including those for insulin, gastrin, growth hormone, adrenocorticotropic hormone and the endorphins, and in the future will undoubtedly shed more light on the structures of their chromosomal genes, the mechanisms regulating their expression, and their evolutionary origins.
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PMID:Formation of biologically active peptides. 610 30

The primary structure of the NH2-terminally extended somatostatins isolated from ovine hypothalamic extracts, one containing 28 residues and the other 25, has been determined. The structure of somatostatin-28 is Ser-Ala-Asn-Ser-Asn-Pro-Ala-Met-Ala-Pro-Arg-Glu-Arg-Lys-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH; the shorter one, somatostatin-25, has the same sequence as somatostatin-28 except that the first three NH2-terminal residues are deleted. The two peptides as isolated were found to be oxidized at the methionine residue to the methionine sulfoxide. Their structures were established by subjecting the native peptides to direct sequence analysis in a Beckman 890C sequencer and identifying the released phenylthiohydantoin derivatives by high-performance liquid chromatography. Their structures were confirmed by trypsin digestion and isolation of all the tryptic peptides, followed by amino acid analysis of the tryptic fragments. Moreover, some of the tryptic peptides were matched with their respective synthetic replicates on high-performance liquid chromatography.
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PMID:Primary structure of ovine hypothalamic somatostatin-28 and somatostatin-25. 610 84

Human stomach, placenta, and amniotic fluid have previously been shown to contain immunoreactive somatostatin (IRS). The present studies were undertaken to further characterize this IRS. Gel chromatography of amniotic fluid revealed only one peak of somatostatin-like immunoreactivity (SLI; mol wt, 15,000) regardless of gestational age. Extracts of human fetal stomach contained three peaks of SLI: 87% of the total IRS coeluted with synthetic tetradecapeptide somatostatin (SRIF), 12% coeluted with synthetic somatostatin-28 (S-28), and 4% coeluted with amniotic fluid SLI. Extracts of 9- to 13-week-old placentas contained 38.9 +/- 5.3 pg IRS/mg protein (range, 21-62 pg IRS/mg protein). Chromatography revealed that 57% of the total IRS coeluted with SRIF, 19% coeluted with S-28, and 23% eluted in a position indicating a molecular weight of 12,000. Serial dilutions of amniotic fluid SLI and material from each peak of stomach and placental SLI showed parallelism with synthetic SRIF. Treatment with 8 M urea and dithiothreitol did not convert any of these SLIs to smaller immunoreactive forms. Incubation of purified amniotic fluid SLI with 1% (wt/wt) L-(tosylamido 2-phenyl)ethyl chloromethyl ketone-trypsin for 90 min resulted in partial conversion to immunoreactive material coeluting with SRIF. When synthetic S-28 was incubated in fresh amniotic fluid at 37 degrees C, it was rapidly degraded (t 1/2 approximately or equal to 25 min). These studies indicate that human amniotic fluid IRS is composed of 15K SLI only, whereas human stomach and placental IRS are heterogeneous, comprising SRIF as well as larger forms of SLI which probably represent SRIF precursors.
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PMID:Evidence for somatostatin precursors in human stomach, placenta, and amniotic fluid. 611 9

Using a new model of a reversible pancreatic fistula which allows the long-term-investigation under nearly physiological conditions on the unrestrained dog, we tested the effect of somatostatin (50 micrograms), calcitonin (4 micrograms), glucagon (1 microgram), and prostaglandin E1 (150 micrograms) on the exocrine pancreatic function in 45 experiments over a period of 13 h: SST inhibits the basal as well as the secretin or CCK-stimulated secretion: calcitonin shows inhibition of the stimulated secretion only; glucagon blocks the secretin-stimulated pancreatic function; and PGE1 reduces the bicarbonate concentration and trypsin output in secretin stimulation, but in one of the two series it stimulates the basal secretion.
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PMID:The effect of SST, glucagon, calcitonin and PGE1 on exocrine pancreatic secretion in the unrestrained dog in long-term experiments. 611 65

Messenger RNA from bovine hypothalami was used to direct the synthesis in vitro of a precursor to somatostatin (SRIF) of Mr 15,500. Specific antibodies, raised against the chemically synthesized tetradecapeptide SRIF-14, were used for the preliminary characterization. The radioactively labelled preprosomatostatin was then cleaved by trypsin or cyanogen bromide and the products were assayed by two-dimensional fingerprinting techniques. The results conclusively demonstrated the presence of the tetradecapeptide SRIF-14 sequence and its naturally occurring N-terminally extended form, SRIF-28. This 28-amino-acid sequence was shown to occupy the C terminus of the 15,500-dalton precursor and is probably preceded by basic amino acid(s).
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PMID:Fingerprint analysis of bovine hypothalamic preprosomatostatin. Identification of somatostatin-28 at the C terminus. 613 Sep 42


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