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)

Previous studies have demonstrated that normal and tumoral pituitaries release in vitro somatostatin (SRIH) and contain messenger RNAs encoding the preproSRIH. In the present study, we document the presence and characterization of the SRIH precursor in a growth hormone (GH)-secreting human pituitary adenoma, using two biochemical procedures: Sephadex G50 filtration and high performance liquid chromatography (HPLC). Sephadex G50 filtration of a 2M acetic acid extract demonstrated the presence of three SRIH-like immunoreactive (SLI) peaks, distinct from SRIH 1-28 and SRIH 1-14 used as standard. Molecular mass of the SLI material present in each peak was estimated as 21, 17 and 12 kilodaltons (kDa). SRIH 1-28 and/or 1-14 were not detected in this extract. Reverse phase HPLC was performed on a C18 column; all the three forms of SLI material coeluted with the rat hypothalamic proSRIH indicating a high homology between the human pituitary proSRIH and that of the rat hypothalamus. These results demonstrate for the first time the presence of high molecular mass proSRIH forms in a GH-secreting pituitary adenoma, and thus enable us to conclude for a local pituitary production of SRIH.
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PMID:[Presence and characterization of somatostatin precursor in human growth hormone secreting pituitary gland tumor]. 167 49

1. A new 17-kDa mammalian ribosomal protein (PR17) was purified to homogeneity from the rat exocrine pancreas. The purification procedure was based on acidic extraction of a heat-denatured homogenate, ammonium-sulfate precipitation, hydrophobic chromatography on phenyl-Sepharose and analytical reverse-phase HPLC on mu Bondapak C18. Fractions of interest were collected using an antiserum directed against the first (1-14) moiety of somatostatin (1-28). 30 micrograms pure RP17 were obtained from 1 g fresh pancreas. 2. A short 111-b cDNA encoding RP17 was amplified from rat pancreatic first-strand cDNA template by using two 64-fold degenerate heptadecamer primers in the DNA-polymerase-chain reaction. From the sequence of amplified cDNA, an unambiguous oligonucleotide probe was designed to screen a rat pancreatic cDNA library. A cDNA clone coding for RP17 was isolated, whose nucleotide sequence, with an open reading frame coding for 155 amino acids (molecular mass of 17,199 Da), confirmed the partial amino acid sequences directly obtained from the purified protein. 3. Northern-blot analysis showed that a similar 0.75-kb transcript was present in rat pancreas, in the rat pancreatic acinar cell line AR 4-2J and in the human neuroblastoma cell-line NB-OK-1, the highest level being in the latter two preparations, despite similar levels of RP17 in all three preparations, as tested with a rabbit antiserum directed against purified RP17. 4. The N-terminal sequence of both RP17 and the ribosomal protein YL43 from Saccharomyces cerevisiae (39 amino acid residues) showed a high degree of identity (77%), indicating that RP17 is a mammalian homolog of yeast ribosomal protein YL43.
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PMID:Purification, primary structure and molecular cloning of a rat ribosomal protein showing homology with yeast ribosomal protein YL34. 173 22

The epoxyeicosatrienoic acids (EETs) were discovered as products of a cyclooxygenase/lipoxygenase-independent, cytochrome P-450 catalyzed metabolism of arachidonic acid (AA) termed the "epoxygenase" pathway. The rat hypothalamus is able to synthesize EETs from exogenous AA, and 5,6-EET has been found to release the neuropeptide somatostatin (SRIF) from hypothalamic nerve terminals of the median eminence (ME). In the present study, hypothalami from male rats were examined for the presence of endogenous EETs, using chemical, chromatographic, and mass spectral analysis procedures. The samples were initially separated in a C18 Sepralyte column, fractionated on TLC plates, and purified by reverse phase HPLC. Thereafter, they were esterified (pentafluorobenzyl esters) and subjected to negative ion chemical ionization/gas chromatography (GC)/mass spectral (MS) analysis. The GC retention time and the MS fragmentation patterns revealed the presence of a mixture of 8,9-, 11,12- and 14,15-EETs; instability of 5,6-EET during the isolation protocol precluded its identification. Total hypothalamic EET concentration was estimated to be 120 ng/g wet tissue. The 8,9-regiosomer released SRIF from ME nerve terminals with an ED50 of 5 x 10(-12) M; Dopamine (DA) and the D2 receptor agonist PPHT, but not the D1 receptor agonist SKF-38393, induced SRIF release from the ME. This effect was blocked by clotrimazole and ketoconazole, two inhibitors of microsomal cytochrome P-450 function and AA epoxygenase in particular. In contrast, the inhibitors failed to affect the increase in SRIF release induced by 8,9-EET. These results indicate that: 1) in addition to cyclooxygenase and lipoxygenase products, epoxygenase metabolites of AA are endogenous compounds of the hypothalamus, and 2) EETs may mediate the increase in SRIF release from hypothalamic neurons induced by the interaction of DA with D2 receptors.
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PMID:Epoxygenase products of arachidonic acid are endogenous constituents of the hypothalamus involved in D2 receptor-mediated, dopamine-induced release of somatostatin. 196 82

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 presence of immunoreactive and biologically active somatostatin in sheep and human milk has been demonstrated. Milk somatostatin exhibits similar chromatographic behavior to that of synthetic somatostatin-14 on both reversed-phase C18 and cation-exchange high-performance liquid chromatography columns. Milk, in contrast to plasma, contains only somatostatin-14-like material. Milk somatostatin was capable of inhibiting the basal and the prostaglandin-induced release of growth hormone from anterior pituitary cell cultures in a pattern similar to synthetic somatostatin-14. The concentrations of the peptide, as determined by radioimmunoassay, were found to be 113 pg/ml in human milk and 150 +/- 4.8 pg/ml (mean +/- range) in sheep milk. These values are severalfold higher than the corresponding concentration of the peptide in the plasma of these species. These findings are analogous to our previous observations concerning two other hypothalamic hormones, luliberin and thyroliberin [Baram, T., Koch, Y., Hazum, E. and Fridkin, M. (1977) Science (Wash. DC) 198, 300-302]. The high concentration of somatostatin and other neuropeptides in milk implies either an active concentrating mechanism in the mammary gland or an additional extrahypothalamic source for the synthesis and release of these peptides.
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PMID:Immunoreactive and biologically active somatostatin in human and sheep milk. 285 95

Acylcarnitines were tested as potential absorption-enhancing agents for drugs that are poorly absorbed from the gastrointestinal tract. Urethan-anesthetized Sprague-Dawley rats and conscious Beagle dogs were used. Palmitoyl-DL-carnitine was the most effective acylcarnitine tested, although significant increases in drug absorption were observed with acylcarnitines containing C12 through C18 fatty acid chains. Palmitoyl-DL-carnitine afforded significant increases in the absorption of cefoxitin, gentamicin, cytarabine, somatostatin analogue, and alpha-methyldopa. The response to palmitoyl-DL-carnitine was concentration dependent and reversible within 60-120 min. Histological examination of the intestinal tissue revealed no apparent change in mucosal structural integrity at doses of palmitoyl-DL-carnitine that resulted in increased drug absorption. The acylcarnitines were effective in increasing drug absorption from the small intestine and the rectal compartment of both rats and dogs. The data also demonstrated effectiveness with aqueous and solid dosage forms (Witepsol H-15 suppositories). The data suggest that acylcarnitines may be effective and safe absorption-enhancing agents for a variety of drugs.
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PMID:Acylcarnitines: drug absorption-enhancing agents in the gastrointestinal tract. 287 54

On forty-six fasting and resting children, aged 5-17 years, with short stature (below -2 SD) a growth hormone releasing hormone (GH-RH) stimulation test (2 micrograms/kg iv bolus, Sanofi) was performed. Twenty-two children were prepubertal, of which, 13 had a constitutional short stature (CSS), nine an idiopathic growth hormone deficiency (IGHD). Twenty-four subjects were pubertal, at the stage II or III of Tanner. Among them, six had a constitutional short stature (CSS) and 18 an idiopathic delayed puberty (IDP). Blood samples were taken for determination of plasma somatostatin-like immunoreactivity (SLI) in chilled test tubes containing EDTA + aprotinin. Plasma SLI levels were measured after extraction and concentration on C18 Sep Pack columns by radioimmunoassay using an antibody against 1-14 somatostatin. The sensitivity of this assay is around 3 pg/ml. After GH-RH stimulation the peak of GH (mean +/- SEM) was in prepubertal subjects: 25.3 +/- 9.1 micrograms/l in CSS, and 18.6 +/- 10.3 micrograms/l in IGHD. In pubertal subjects GH peaks were 17.6 +/- 8.4 micrograms/l in CSS and 15.6 +/- 3.8 micrograms/l in children with IDP. No significant differences was found between basal plasma SLI levels in the four groups of subjects, being respectively (mean +/- SEM) 11.9 +/- 1.8 pg/ml in prepubertal subjects with CSS, 9.6 +/- 2.6 pg/ml in IGHD, 7.6 +/- 1.7 pg/ml in pubertal children with CSS and 6.6 +/- 1.5 pg/ml in children with IDP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Negative correlation between peripheral plasma somatostatin levels and GH responses to GH-RH stimulation tests in children. 287 69

In most patients with acromegaly basal serum GH concentrations are elevated and remain above 5 micrograms/L after oral glucose administration. In some patients, however, serum insulin-like growth factor I (IGF-I) concentrations are elevated with only minimal elevations of serum GH. We studied the serum GH and IGF-I of two such patients to determine whether these peptide hormones are normal in this clinical situation. The serum GH of these patients was found to bind normally to receptors of the IM-9 lymphocyte. The elution pattern of IGF-I extracted from the patients' serum was similar to that of (Thr59) human IGF-I after passage through a Bio-Rad P-60 column in 0.5 M acetic acid. The IGF-I was further characterized by isoelectric focusing and C18 reverse phase high pressure liquid chromatography (HPLC). The isoelectric points of the IGF-I components were similar to those of IGF-I in normal serum. The IGF-I in one patient had two components by HPLC, while that of the other patient had only one major component. The IGF-I components isolated by HPLC were normally active in stimulating [3H] alpha-aminoisobutyric acid uptake by normal human fibroblasts. The elevated serum IGF-I concentrations of these two patients were GH dependent. Transsphenoidal adenomectomy in one patient resulted in a decline in serum IGF-I to a high normal concentration. Lowering the serum GH to subnormal concentrations by the administration of the somatostatin analog SMS 201-995 (Sandoz) restored normal IGF-I concentrations in the second patient. We conclude that the GH and IGF-I of these two patients cannot account for their apparent enhanced GH responsiveness.
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PMID:Characterization of serum growth hormone (GH) and insulin-like growth factor I in active acromegaly with minimal elevation of serum GH. 365 10

L[35S]Cys-arginine vasopressin, -oxytocin, and -somatostatin were purified from hypothalami and neurohypophyses 4 h after rats received L[35S]Cys via the third ventricle. After acetic acid extraction, Sephadex G-25 filtration, and chemoadsorption to C18-silica (Sep-Pak cartridges), the labeled peptides were rapidly separated by gradient elution, reversed phase, high pressure liquid chromatography (HPLC). The identity and isotopic purity of the labeled peptides were determined by several reversed phase HPLC procedures in conjunction with chemical modification. The labeled peptide fractions were at least 50% radiochemically pure. Using this HPLC isolation procedure, incorporation of L-[35S]Cys into each peptide was determined n hydrated and dehydrated rats. Label incorporation into arginine vasopressin and oxytocin in the hypothalamus and the neurohypophysis of dehydrated rats was 2-3 times greater than that in hydrated rats. Incorporation of label into hypothalamic and neurohypophyseal somatostatin was unaffected by the hydration state of the animal. This procedure thus provides a very rapid, but sensitive, set of techniques for studying the control of small peptide biosynthesis in the brain.
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PMID:In vivo biosynthesis of L-[35S]Cys-arginine vasopressin, -oxytocin, and -somatostatin: rapid estimation using reversed phase high pressure liquid chromatography. 611 94

The preferred radiotracer for use in radioimmuno- and receptor assays is one which is as similar as possible to the native hormone in both physicochemical and biological properties. Until recently, rapid detailed evaluation of iodination methodology as well as separation of site-specific tracers and their evaluation relative to the native protein has not been possible. Using reversed-phase high-performance liquid chromatographic methodology (C8 or C18 columns) we have evaluated a variety of iodination techniques and conditions. Procedures were found that allow the isolation of site-specific radiolabelled protein hormones in a rapid, reproducible and quantitative manner. The radiotracers are of the highest possible specific activity, have very low levels of damage and are more stable than tracers prepared by conventional techniques. This methodology has been applied to preparing tracers of beef, pork and human insulins, proinsulins and C-peptides as well as analogues of these proteins. In addition, the methodology has been applied to somatostatin, glucagon, pancreatic polypeptide, vasoactive intestinal peptide and luteinizing hormone-releasing hormone. The use of these tracers yielded increased sensitivity and reproducibility in a number of radioimmunoassays (e.g. C-peptide and glucagon), more reproducible results in radioreceptor assays (e.g. insulin receptors) and more defined studies on drug absorption and degradation. Finally, scale-up of our isolation procedures has yielded the 127I-analogue for homologous binding and displacement studies.
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PMID:High-performance liquid chromatographic preparation of single-site carrier-free pancreatic polypeptide hormone radiotracers. 635 32


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