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)

Eleven continuous cultures of human pulmonary small cell carcinoma cells were examined, and eight were shown to secrete quantities of somatostatin-like immunoreactivity (SRIF-LI) ranging from 0.07-27 ng/ml culture medium/4 days, SRIF-LI was also found in a 2-N acetic acid extract of one of three human pulmonary small cell carcinomas obtained at autopsy as well as in the extract of a solid tumor resulting from inoculation of nude, athymic mice with SRIF-LI-producing, cultured small cell carcinoma cells. The SRIF-LI produced by one continuous cell line, DMS 53, was characterized in terms of its immunological, chromatographic, and biological properties. SRIF-LI from DMS 53 culture media and lysed cells was heat stable and exhibited parallel displacement to synthetic SRIF standard in a double antibody RIA. DMS 53 SRIF-LI was quantitatively retained on an immunoaffinity column of sheep anti-SRIF-Sepharose 4B under neutral conditions and could be eluted with 2 N acetic acid. Gel filtration chromatography of immunoaffinity-purified SRIF-LI revealed multiple molecular weight forms, the largest of which had an apparent molecular weight of 10,000-12,000 daltons and may represent a precursor form. This high molecular weight SRIF-LI form was resistant to exposure to denaturing conditions (8 M urea or 4 M urea plus 0.5% mercaptoethanol), suggesting the absence of noncovalent and/or disulfide linkages. A low molecular weight form coeluted with synthetic SRIF. Additional evidence for the identity of this form with the tetradecapeptide was provided by highly specific reverse phase high performance liquid chromatography. The rate of degradation of high molecular weight SRIF-LI by the cultures was markedly reduced in comparison to that of the SRIF monomer, resulting in a preferential accumulation of high molecular weight SRIF-LI in 4-day culture medium. Bioactivity of DMS 53 SRIF-LI was assessed in 4-day primary monolayer cultures of rat adenohypophyseal cells where 10(-10)-10(-9) M synthetic SRIF elicited a linear log-dose suppression of 5 X 10(-4) M synthetic SRIF elicited a linear log-dose suppression of 5 X 10(-4) M dibutyryl cAMP-stimulated rat GH release. Immunoaffinity-purified SRIF-LI from DMS 53 lysed cells and 1-h serum-free incubation medium, which consisted predominantly of monomeric SRIF, was equipotent to synthetic SRIF, SRIF-LI from 4-day culture medium consisted mostly of the high molecular weight form and exhibited a reduced bioassay potency ratio relative to synthetic SRIF of 0.73 (95% confidence limits, 0.99-0.53). Chromatographically purified high molecular weight SRIF-LI had significant bioactivity with a bioassay to immunoassay ratio of 0.19 (95% confidence limits, 0.33-0.09). The demonstration of ectopic SRIF, production by human pulmonary small cell carcinoma is consistent with the proposed derivation of this tumor from a cell type in the amine precursor uptake and decarboxylation cell series.
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PMID:Ectopic production of somatostatin-like immuno- and bioactivity by cultured human pulmonary small cell carcinoma. 610 52

Somatostatin-like immunoreactivity (SLI) of plasma from the portal vein, aorta, and inferior vena cava and of lymph from the thoracic duct of both fasted and meal-stimulated dogs was measured and characterized with respect to molecular size. Significant portal vein-arterial and arteriovenous SLI gradients were present in fasting dogs, and they increased sharply after the intragastric infusion of liver extract and HCl. Chromatography of fasting plasma at pH 7.4 revealed all measurable SLI to be confined to the void volume fractions of a Bio-Gel P-6 column, although, after a 7-fold concentration of fractions coeluting with somatostatin, approximately 1600-daltion SLI was detected in the portal venous plasma. The rise in SLI after a meal was due primarily to an increase of approximately 1600-dalton SLI; approximately 1600-dalton SLI was detectable in unconcentrated portal venous and aortic plasma and in the peripheral venous plasma concentrated 7-fold. SLI levels in lymph were similar to those of basal venous plasma and did not increase with a meal. This first demonstration at a physiological pH of a approximately 1600-dalton SLI in the arterial circulation suggests that a free, readily available form of endogenous somatostatin is present in the canine circulation and could be playing a hormonal role.
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PMID:Free somatostatin in the circulation: amounts and molecular sizes of somatostatin-like immunoreactivity in portal, aortic, and vena caval plasma of fasting and meal-stimulated dogs. 610 41

We have recently reported the establishment of 16 series of calcitonin-producing transplantable rat medullary thyroid carcinoma. In the present study, these tumor series have been evaluated for the presence of somatostatin-like immunoreactivity. Each of the series contained detectable levels of both peptides. Immunoreactive somatostatin varied from less than 1 ng/mg of protein to almost 500 ng/mg of protein. The range of immunoreactive calcitonin was 0.3 to 30 micrograms/mg of protein. Although somatostatin-like immunoreactivity was always less than that of calcitonin, the levels in certain series were as high as those found in neural or endocrine tissues used for in vitro studies of somatostatin elaboration. No significant correlation was found between tissue levels of these two peptides. Two tumor lines were generated by initiation of tumor growth with cells from primary monolayer cultures. Levels of both immunoreactive calcitonin and somatostatin significantly differed from those of the parent lines, which were maintained by serial passage of tissue fragments only. Plasma somatostatin-like immunoreactivity assessed in two tumor series with high (149 ng/mg of protein) and low (1.5 ng/mg of protein) tissue levels was 3100 and 50 pg/ml, respectively. Gel filtration chromatography of tissue and blood extracts showed a predominant peak (greater than 90%) of immunoreactive somatostatin eluting at the position of the native hormone. Three other peaks were resolved in the tissue extract with estimated molecular weights of 14,000, 8,700, and 5,000. The high level of somatostatin-like immunoreactivity and the presence of multiple large forms suggest that certain tumor lines will prove valuable for studies of somatostatin biosynthesis and secretion.
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PMID:Tumor and plasma somatostatin-like immunoreactivity in transplantable rat medullary thyroid carcinoma. 611 Apr 76

Ectopic secretion of somatostatin in one patient with a thymic tumour and in two patients with lung tumours is described. All three patients also had ectopic ACTH secretion. Gel filtration chromatography under dissociating conditions showed the two lung tumour extracts to contain predominantly 1600 MW somatostatin monomer while the thymic tumour contained predominantly a 3000-3500 MW form of somatostatin, 77% of which was not converted to 1600 MW somatostatin by dithiothreitol (an agent which reduces disulphide bridges). This form may therefore represent a covalently-bound precursor of somatostatin rather than a dimer of two somatostatin monomers. Plasma from all three tumour patients and from normal subjects contained both 1600 and 3000--3500 MW somatostatin. It is suggested that somatostatin secretion may frequently be associated with multiple hormone producing tumours.
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PMID:Somatostatin secretion by lung and thymic tumours. 611 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

To characterize the glucagon released in response to epineephrine in depancreatized dogs, plasma samples before and during epinephrine infusion were subjected to molecular-sieve chromatography on Bio-Gel P-30 columns. The chromatographic profile for extrapancreatic immunoreactive glucagon (eIRG) revealed two glucagon moieties of molecular weight 9,000 to 12,000. GLI of this molecular weight was released in response to epinephrine only under conditions of prevailing hyperglycemia. To determine if glucagon's participation in epinephrine-induced hepatic glucose overproduction in diabetes was dependent upon the degree of metabolic control, six conscious depancreatized dogs were infused with epinephrine or epinphrine plus somatostatin, under conditions of prevailing hyperglycemia or normoglycemia. Under normoglycemic conditions, epinephrine stimulated eIRG release, but there was a similar rise in hepatic glucose production (Ra) with or without glucagon suppression by somatostatin. Under hyperglycemic conditions, epinephrine stimulated eIRG and GLI release, and the rise in Ra was significantly greater with epinephrine than with epinephrine plus somatostatin infusion. Thus, under conditions of good metabolic control, epinephrine increased hepatic glucose production independently of glucagon, whereas with poor metabolic control, glucagon contributed to hepatic overproduction of glucose.
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PMID:Chromatographic pattern of extrapancreatic glucagon and glucagon-like immunoreactivity before and during stimulation by epinephrine and participation of glucagon in epinephrine-induced hepatic glucose overproduction. 611 73

The technique of push-pull perfusion was combined with a sensitive somatostatin RIA to determine in vivo immunoreactive somatostatin (IRS) release from the median eminence (ME) of the freely behaving rat. IRS release was compared to plasma GH levels. Concentrations of IRS in ME perfusates indicated pulsatile release, with an interpeak interval of about an hour. In rats with normal plasma GH pulses and normal plasma PRL levels, IRS secretion ranged from 10-100 pg/15 min. In rats with suppressed GH secretion and high plasma PRL levels, IRS secretion was greater, ranging between 50-500 pg/15 min. A rise in the level of IRS in the ME perfusate often coincided with an increase in GH levels in plasma, suggesting that somatostatin may act by a short-loop negative feedback mechanism to regulate GH release. Gel chromatography of IRS from the perfusate suggested that somatostatin is released in more than one molecular weight form.
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PMID:Pulsatile somatostatin release from the median eminence of the unanesthetized rat and its relationship to plasma growth hormone levels. 611 62

We have compared the metabolism of infused somatostatin 14 (SS14) and somatostatin 28 (SS 28) in anesthetized dogs. After iv infusion of either peptide, plasma SS-like immunoreactivity (SLI) coeluted from Bio-Gel P10 columns with the corresponding synthetic peptide marker. The hepatic extraction, renal extraction, MCR, and plasma half-life of plasma SLI and after SS28 infusion were 11.0 +/- 1.5%, 50 +/- 4.8%, 9.9 +/- 1.4 ml/kg.min, and 2.8 +/- 0.3 min, respectively. Corresponding values after SS14 infusion were 43.1 +/- 7.4%, 82.2 +/- 6.6%, 21.9 +/- 6.5 ml/kg.min, and 1.7 +/- 0.2 min. These differences between SS28 and SS14 were all statistically significant (P less than 0.05). When equimolar amounts of each peptide were given as bolus injections, both led to a significant reduction in portal venous blood flow. After the injection of SS14, the reduction in flow was short-lived and returned to baseline by 4 min. However, between 2-7.5 min after the injection of SS28, the reduction in blood flow was significantly greater than that induced by SS14, and returned to baseline only by 15 min. These studies indicate that the metabolism of plasma SLI is significantly slower during the steady state infusion of SS28 in pharmacological doses than after similar infusions of SS14. SS28 led to a more prolonged reduction in portal blood flow than SS14; this effect is probably due to its slowed metabolism. This suggests that further modification of the SS28 molecule may increase its therapeutic potential by slowing its in vivo metabolism.
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PMID:The in vivo metabolism of somatostatin 28: possible relationship between diminished metabolism and enhanced biological action. 612 5

Gel-filtration chromatography of an acid-extract of a phaeochromocytoma, under dissociating conditions, revealed 4 peaks of immunoreactive somatostatin (IRS) of approx. 8-10 kilodaltons (K), 6K, 3.5K and 1.6K as detected by an antiserum (R9) directed against the central region of tetradecapeptide somatostatin (S14). The 3.5K and 1.6K forms of IRS co-eluted with synthetic cyclic S28 and S14 respectively on reversed phase HPLC. Using another radioimmunoassay for the 1-14 sequence of S28 (N-peptide) a peak of immunoreactive N-peptide (IRN) with a molecular weight of approx. 4500 was observed. The antiserum (N3) used in the N-peptide assay was raised against N-Tyr N-peptide and cross-reacts less than 5% with synthetic S28. Two peaks were further characterised by partial tryptic digestion and gel-filtration chromatography. The 3.5K IRS peak was partially converted to a 1.6K IRS form together with an approximately equimolar amount of IRN with apparent molecular weight of 2500. This 2.5K IRN co-eluted both with N-Tyr N-peptide and with the IRN generated by tryptic digestion of synthetic cyclic S28. No IRN peak of this size was observed in the original extract. Tryptic digestion of the 6K IRS peak generated 3.5K and 1.6K IRS and 2.5K IRN. These results suggested that (1) this human phaeochromocytoma contains IRS very similar to the known structure of ovine and porcine S28 and S14. (2) The 6K IRS is composed of an unknown peptide sequence attached via trypsin-susceptible bond to the N-terminus of S28. (3) In this tumour S14 is being generated directly from 6K IRS and not via S28.
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PMID:Evidence for direct production of somatostatin-14 from a larger precursor than somatostatin-28 in a phaeochromocytoma. 613 17

The cytosol fraction of rat pancrease can bind [3H] estradiol specifically and extensively. In contrast to the rat uterus, the binding protein in pancreas requires an accessory factor as a coligand in the steroid-binding reaction. Removal of this accessory factor by passage of the cytosol through CM Affi-Gel blue columns renders eluate fractions virtually incompetent with respect to binding of [3H]estradiol (10 nM). Certain synthetic oligopeptides such as N-benzoyl-L-argininyl-p-nitroanilide, as well as an endogenous accessory factor, can reactivate binding of [3H]estradiol. Thus, localization of the protein that binds [3H]estradiol following chromatography with CM Affi-Gel blue columns can be determined readily by assaying eluate fractions in the absence and presence of either accessory factor or N-benzoyl-L-argininyl-p-nitroanilide. Addition of somatostatin (tetradecapeptide referred to as SRIF14; somatotropin release inhibiting factor) to the activatable, but incompetent, eluate fractions, also enhanced binding of [3H]estradiol. The effect of SRIF14 was biphasic. The threshold concentration required for activation of [3H]estradiol binding was about 1 microM, and maximal stimulation occurred at 25 microM. At higher concentrations of SRIF14, binding declined and reached basal levels at about 75 microM. The concentrations of somatostatin required for activation of binding of [3H]estradiol in vivo may be lower than those indicated above since 1) preparations containing [3H]estradiol-binding protein also contained an SRIF14 peptidase. Following incubation of [125I-Tyr1]SRIF14 with these preparations there was loss of binding of radiolabeled peptide with SRIF14 antiserum. 2) The biphasic nature of SRIF14 activation may reflect feedback inhibition of [3H]estradiol binding by a degradation product of SRIF14. Since SRIF14 has been identified in the delta- (or D-) islet cells of the pancreas, and in concentrations that may be in the microM range, the possibility is raised that these cells serve a paracrine function with respect to acinar cell secretion.
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PMID:Somatostatin enhances binding of [3H]estradiol to a cytosolic protein in rat pancreas. Possible role of oligopeptide coligands in secretion. 613 21


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