UNIPROT:P61278 - FACTA Search

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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription of proto-oncogene fos is induced by elevated levels of intracellular cAMP. We report that human c-fos promoter recombinants transfected into rat pheochromocytoma cells (PC12) and human choriocarcinoma cells (JEG-3) are induced by stimulation of adenylate cyclase and that this induction is diminished considerably in the mutant PC12 cell line A126-1B2, which is deficient in cAMP-dependent protein kinase II. An element centered at position -60 of the c-fos promoter, which encompasses a consensus cAMP response element (CRE), is sufficient to confer cAMP responsiveness to a herpes thymidine kinase/CAT fusion gene. The specific binding of a nuclear protein to the c-fos CRE can be competed by the somatostatin and alpha-chorionic gonadotropin (alpha-CG) promoter regions that contain CREs. Gel mobility shift assays with double-stranded oligonucleotides containing either the wild-type or mutated c-fos CRE sequence have demonstrated that binding occurs only to the wild-type CRE. The nuclear factor binding to the c-fos CRE is likely to be transcription factor CREB (CRE nuclear binding protein), because an affinity-purified 43-kD CREB isolated from PC12 cells binds efficiently in a DNA footprinting assay. Thus, regulation of the c-fos gene transcription appears to involve a mechanism common to many genes that respond to cAMP as a second message leading to cell growth and differentiation.
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PMID:Induction of proto-oncogene fos transcription through the adenylate cyclase pathway: characterization of a cAMP-responsive element. 285 Sep 67

Acute effects of somatostatin analog (SMS 201-995) on pancreatic hormones were studied in two patients with malignant islet-cell carcinoma. Before and after subcutaneous injection of somatostatin with a doses of 50 micrograms, blood glucose (BG), serum growth hormone (hGH), C-peptide immunoreactivity (CPR), plasma immunoreactive glucagon (IRG) and gastrin were assayed, and changes in elution patterns of IRG and gastrin were also analyzed on Bio-Gel P-30 column chromatography. In Patient 1 with glucagonoma syndrome and hypergastrinemia, a prompt and remarkable decrease in plasma IRG and gastrin was observed after the injection of SMS 201-995 in association with a decrease in blood glucose, and then IRG and gastrin increased gradually. The suppressive effect continued for at least 6 hours. On gel filtration of the plasma obtained before the injection of the analog, three major peaks, greater than 20000, 9000 and 3500 molecular-weight (mol wt) fractions, were seen in IRG fraction. The decrease in plasma IRG observed at 1 hour after the injection was mainly due to a marked decrease in the 3500 molecular weight fraction. In addition, a slight decrease in the 9000 mol wt fraction was seen. At 4 hours after the injection, the 3500 mol wt peak returned to the previous level, while the 9000 mol wt peak decreased further. On the other hand, the gastrin elution pattern of plasma obtained before the injection revealed three major gastrin peaks, greater than 20000, 7000 and 5000 mol wt fraction. The changes in the gastrin elution pattern after the injection were similar to those of the IRG elution pattern. In Patient 2 with Zollinger-Ellison's syndrome, the plasma gastrin level decreased gradually for 5 hours after the injection. On gel filtration of the plasma obtained before the injection, two major gastrin peaks, 7000 and 5000 mol wt fraction, of which the large-molecular fraction was more prominent than the small-molecular fraction, were observed. After the injection, a marked decrease in the small-molecular fraction and a gradual decrease in the large-molecular fraction were observed for 4 hours, accompanied by a decrease in plasma gastrin. At 7 hours after the injection, the smaller fraction was augmented again. The serum CPR and hGH was slightly suppressed after the injection in both patients. The adverse effects of slight nausea and vomiting were noticed only in Patient 1.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Inhibitory effects of somatostatin analog (SMS 201-995) on pancreatic hormones in patients with malignant islet-cell carcinoma]. 285 26

Extracts of Escherichia coli grown in defined medium contain somatostatin-related material (1-10 pg/g wet weight of cells). Preconditioned medium had no immunoactive somatostatin whereas, conditioned medium had 110-150 pg/l. Following purification of the extracted material on Sep-pak C18, Bio-Gel P-6 and HPLC, multiple molecular weight forms of somatostatin- (SRIF-) related material were identified. The material in one peak reacted in both the N-terminal and C-terminal SRIF immunoassay and coeluted on HPLC with SRIF-28, whereas that in a second peak eluted near SRIF-14 and was reactive only in the C-terminal SRIF assay. The two peaks are thus similar to SRIF-28 and SRIF-14 of vertebrates. These findings add support to the suggestion that vertebrate-type peptide hormones and neuropeptides have early evolutionary origins.
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PMID:Evidence for multiple molecular weight forms of somatostatin-like material in Escherichia coli. 285 77

The hepatic clearances of somatostatin (SS)-28 and SS-14 by the perfused rat liver were compared, using a recirculating, plasma-free, erythrocyte-containing perfusion system. The disappearance rate constant, half time, clearance, and hepatic extraction ratio when 1.2 nM SS-28 was added to the perfusate were 0.0221 +/- 0.0051 min-1, 36.6 +/- 7.6 min, 0.34 +/- 0.08 mL/min, and 17.2 +/- 3.9%, respectively. The corresponding values obtained when SS-14 was added to the perfusate were 0.0405 +/- 0.0022 min-1, 17.3 +/- 1.0 min, 0.71 +/- 0.05 mL/min, and 35.4 +/- 2.6%, respectively. The differences between the SS-28 and SS-14 indices were all statistically significant. In addition, the perfusates with SS-28 added were eluted on Sephadex G-25 fine columns and somatostatinlike immunoreactivity (SLI) was determined. No SS-14 was found in perfusate containing SS-28 at both 5 and 30 min after the beginning of the perfusion. To investigate whether or not the liver plays an important role in the clearance of SS-28 or the conversion of SS-14 in vivo, the plasma disappearance of 2 micrograms SS-28 was compared in the whole rat and the functionally hepatectomized model. The half time of plasma SS-28 was 1.43 +/- 0.12 min in the whole rat, significantly shorter than the 2.20 +/- 0.14 min in the hepatectomized model. Gel filtration of plasma extract samples at 0.5 min after the SS-28 injection showed two major peaks of SLI: a first peak corresponding to SS-28 and a second peak coeluted in the position of SS-14 in both the whole rat and the hepatectomized model. At 4 min after the SS-28 injection, the first peak disappeared and only a small second peak was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of somatostatin-28 and somatostatin-14 clearance by the perfused rat liver. 285 4

The main purpose of the present study was to characterize the tissue and releasable molecular forms of somatostatin-28[1-12]-like immunoreactivity (S-28[1-12]LI) in rat median eminence (ME) fragments and to compare them with somatostatin-14-like immunoreactivity (S-14 LI) forms. Acetic acid extracts of ME were fractionated on Sephadex G-50 columns (in 6 M urea). The column eluate was monitored for S-28[1-12] LI by RIA with antibody R21 which detects S-28[1-12], S-28, and higher molecular weight forms of S-28[1-12] LI, but not S-14. The S-14 LI RIA utilized recognizes S-14, S-28, and prosomatostatin (pro-S). Rat ME contained 221 +/- 25 pmol S-14 LI/mg protein and 407 +/- 51 pmol S-28[1-12] LI/mg protein. By gel filtration S-14 LI was resolved into three peaks corresponding to S-14, S-28, and a higher mol wt form (14,000) corresponding to pro-S. S-28[1-12] LI consisted of at least five forms corresponding to pro-S, S-28, S-28[1-12], a form which represented pro-S without the S-14 sequence, and a form slightly smaller than S-28[1-12]. Pools of 20 ME incubated in 56 mM K+ solution showed 4.6-fold Ca++-dependent release of S-14 LI and 4-fold release of S-28[1-12] LI. Gel chromatographic analysis of the released material showed all three tissue S-14 LI forms and each of the tissue S-28[1-12] LI forms. HPLC analysis and RIAs further confirmed the release of S-14, S-28, S-28[1-12], and the S-28[1-12] LI form smaller than S-28[1-12]. These data suggest the presence of at least six molecular forms of somatostatin in ME. The release of this large number of peptides, presumably from mature secretory granules in ME in response to depolarization, suggests that they are products of the normal posttranslational processing of pro-S.
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PMID:Characterization of tissue and releasable molecular forms of somatostatin-28[1-12]-like immunoreactivity in rat median eminence. 285 91

The presence of multiple forms of somatostatin-like immunoreactivity (SSLI) in the rat hypothalamus was confirmed using a sensitive radioimmunoassay in conjunction with gel filtration chromatography and high performance liquid chromatography (HPLC). Gel filtration chromatography of hypothalamic extracts revealed the presence of four forms of SSLI with estimated molecular weights of 1500, 3000, 6000 and 10000. Analysis by HPLC indicated that the 1500 and 3000 mol. wt forms of SSLI corresponded respectively to somatostatin-14 (SS14) and somatostatin-28 (SS28) whereas the 6000 and 10000 mol. wt forms eluted together as a composite peak of high molecular weight somatostatin (HMW-SS). The proportions of SS14 (63%), SS28 (12%) and HMW-SS (25%) present in the hypothalamus were similar to those in the amygdala (59, 9 and 32% respectively). In contrast, the median eminence contained a greater proportion of SS28 than the other tissues: SS14, SS28 and HMW-SS were present in the proportions 40: 24: 26%. These results show that the rat median eminence differs from the hypothalamus as a whole in containing SS14 and SS28 in almost equimolar concentrations. The localized abundance of SS28 in the nerve terminals of the median eminence suggests a specific role for this peptide in the hypothalamic regulation of growth hormone secretion.
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PMID:Multiple forms of somatostatin-like immunoreactivity in the hypothalamus and amygdala of the rat: selective localization of somatostatin-28 in the median eminence. 286 Jan 97

Previous studies have shown that somatostatin-14 (S-14) is rapidly metabolized in the liver through the action of aminopeptidases and endopeptidases, resulting in separate cleavages at the N-terminus and the cyclized (ring) portion of the molecule. In the present study we have characterized the hepatic metabolism of somatostatin-28 (S-28) and compared it with that of S-14 to determine whether S-28 is degraded by a process similar to that for S-14, and additionally, whether the hepatic metabolism of S-28 results in significant conversion to S-14. Isolated rat livers were perfused with synthetic S-28, somatostatin-25[(S-25), an N-terminal metabolite of S-28], C- and N-terminally radioiodinated analogs of S-28, S-14, and des-Ala1-S-14[(S-13), an N-terminal metabolite of S-14]. The metabolic products were characterized by separate N-terminally directed S-14 and S-28 RIAs, a common ring-directed RIA for S-14, S-28, S-13, and S-25, immunoprecipitation, gel chromatography, and HPLC. Hepatic extractions of S-28 and S-25, monitored as ring-directed immunoreactivity, were equivalent, but both occurred 4 times more slowly than that of S-14 or S-13. By contrast, the N-terminal metabolism of S-14 and S-28 monitored by specific N-terminal RIAs occurred at similar rates (hepatic extraction of 54% and 44%, respectively). Both S-14 and S-28 were degraded significantly more rapidly at the N-terminus than at the ring segment. Immunochemical characterization of the radioactive metabolites of N- and C-terminally radioiodinated S-28 analogs confirmed the more rapid N-terminal cleavage of S-28 compared with its ring breakdown. Gel chromatography of S-28 perfusates followed by RIA of the column fractions for N-terminal and ring-reactive metabolites, showed a time-dependent conversion of S-28 to a peak coeluting with S-14 (27% conversion by 60 min). That S-14 was a significant metabolite of S-28 was further confirmed by HPLC analysis of the hepatic perfusate. The main hepatic metabolite of S-28 coeluted with S-28 on Sephadex columns but showed reduced N-terminal reactivity compared to intact S-28. This product thus appeared to be a N-terminally modified form of S-28 as also suggested by HPLC analysis where it coeluted with synthetic S-25. These data have demonstrated that the hepatic metabolism of S-28 occurs via three separate processes, two of which are similar to those for S-14. These include 1) endopeptidase cleavage through the cyclized (ring) segment; 2) N-terminal aminopeptidase cleavage to yield metabolites such as S-25; and 3) tryptic-like cleavage of the Arg-Lys region of S-28 to generate S-14.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hepatic metabolism of somatostatin-14 and somatostatin-28: immunochemical characterization of the metabolic fragments and comparison of cleavage sites. 286 Oct 82

The present study was designed to compare, in lean and obese nondiabetic subjects, basal and postprandial levels of peripheral venous plasma insulin, glucagon, gastrin, pancreatic polypeptide (PP), glucose, triglycerides, and somatostatin-like immunoreactivity (SLI) during the infusion of synthetic somatostatin-14 or saline. Thirty-five minutes before the ingestion of the test meal, an infusion of synthetic somatostatin-14 was started at a rate of 0.5 ng/kg X min and was increased to 1.0 ng/kg X min 30 min after consumption of the meal and lasted for another 90 min. During the infusion of saline, basal peripheral vein levels of insulin, gastrin, and triglycerides were elevated in obese subjects, whereas basal plasma SLI levels were significantly lower compared with the lean controls. Basal glucagon and PP levels were similar in both groups. After the ingestion of the meal, augmented concentrations of insulin and gastrin were observed in the obese subjects, whereas postprandial SLI and PP levels were reduced. Chromatography of fasting plasma revealed all measurable SLI to be confined to the void volume fractions of a Bio-Gel P-10 column. The rise in SLI after the meal was due to an increase of SLI co-eluting with somatostatin-28 and somatostatin-14. During the infusion of somatostatin, only basal insulin levels were significantly lower in the obese subjects, whereas no change of any basal hormone level was observed in the lean group. During the infusion of somatostatin, SLI levels were elevated by 20-30 pg/ml in both groups compared with the saline controls. During the infusion rate of 0.5 ng/kg X min, only postprandial PP levels were reduced significantly in the obese group, while all the other parameters were unaffected in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of low-dose somatostatin infusion on pancreatic and gastric endocrine function in lean and obese nondiabetic human subjects. 286 Nov 27

Release of plasma ACTH- and beta-endorphin (beta-EP)-like immunoreactivity (LI) was studied in vivo in a patient with an ectopic ACTH-producing malignant thymoma. Administration of lysin vasopressin stimulated concomitant release of plasma ACTH- and beta-EP-LI. Administration of cyproheptadine, naloxone, and somatostatin significantly suppressed plasma levels of ACTH- and beta-EP-LI, while saline infusion did not. Gel exclusion chromatography of the plasma extracts revealed that ACTH-LI consisted of two components, large and small molecular weight form, while beta-EP-LI consisted of three components, large molecular weight, beta-lipotropin-, and beta-EP-sized form; each of these components was incompletely suppressed by somatostatin infusion. It is suggested that certain tumors may have acquired aberrant multiple receptors during malignant transformation which may lead to the paradoxical hormone response as demonstrated in this case.
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PMID:Concomitant suppression of plasma ACTH- and beta-endorphin-like immunoreactivity by cyproheptadine, naloxone, and somatostatin in the ectopic ACTH syndrome. 286 Nov 53

Extracts of brain, stomach, pancreas, and intestine from Torpedo marmorata, an elasmobranchian cartilaginous fish, contained somatostatin-like immunoreactivity. Gel filtration studies demonstrated that material with the elution volume of somatostatin-14 was the only component detected in all tissue extracts. This result contrasts with the situation in mammals where prosomatostatin is processed to multiple molecular forms in a tissue-specific manner. Somatostatin from pancreas and gut was purified to homogeneity and amino acid sequence analysis indicated that T. marmorata somatostatin from both tissues has the same structure as somatostatin-14 isolated from the higher vertebrates. Further examination of other lower vertebrate species is required in order to test the hypothesis that the ability to regulate the production of multiple forms of a regulatory peptide from a single precursor molecule developed only relatively late in evolution.
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PMID:An elasmobranchian somatostatin: primary structure and tissue distribution in Torpedo marmorata. 286 3

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