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)

Recently, we have reported in immature female rats that short-term blockade of glutamate receptors of the N-methyl-D-aspartic acid (NMDA) subtype by the noncompetitive antagonist MK-801 induced a reduction of growth rate, basal and stimulated growth hormone (GH) release and plasma somatomedin C levels. In the present study, we investigated in immature male rats the mechanism(s) through which agonists and antagonists of glutamate receptors affect GH secretion. In 21-day-old male rats, administration of MK-801 (0.2 mg/kg i.p.b.i.d.) for 10 days induced a significant impairment of growth rate, which was unrelated to a significant reduction of food intake. GH secretion from anterior pituitary fragments of MK-801-treated rats was not significantly reduced under basal conditions but was significantly less under stimulation by 40 mM K+. Incubation of dispersed pituitary cells of 31-day-old rats with N-methyl-aspartic acid (1 and 100 microM), alone or associated with MK-801 (1 microM) did not change GH secretion. Semi quantitative densitometric analysis of hypothalami of MK-801-treated rats evidenced a clearcut decrease in the intensity of GHRH-like immuno-reactivity (LI) staining in the median eminence (ME), whereas no difference was observed in the ME-somatostatin (SS)-LI. Finally, GHRH mRNA but not SS-mRNA, evaluated by slot-blot hybridization, was reduced in the hypothalamus of MK-801-treated rats. These and our previous data would demonstrate that NMDA glutamate receptors play an important role in the neuroendocrine control of GH secretion in the rat, and suggest an action mediated by GHRH-secreting neurons.
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PMID:Central mechanisms subserving the impaired growth hormone secretion induced by persistent blockade of NMDA receptors in immature male rats. 134 48

Neuroblasts obtained from 17 day old rat embryos were incubated for 8 days, after which half of them were treated with 10(-6) M FACE (a mixture of amino acids high in glycine, alanine and aspartic acid), and the other half were left as controls. At the end of 20 days, levels of somatostatin (SRIF) were over 6,000 pg/plate in neuroblasts treated with FACE, versus 500 pg/plate in controls. At this time vasoactive intestinal peptide (VIP) levels were over 230 pg/plate in the FACE treated cultures, while their controls contained less than 150 pp/plate. Protein totals were similar (about 1,000 micrograms/plate) in all FACE treated cultures and controls, indicating that increases in SRIF and VIP were not determined by changes in cell population, but by their synthetic and/or secretory activities triggered by minute amounts of FACE. These results may be of interest in the understanding of Alzheimer's disease.
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PMID:Secretions of somatostatin and VIP in cultures of fetal rat neuroblasts increased by amino acids. 196 11

Prosomatostatin (pro-SS) is a peptide of 92 amino acids which contains the extensively studied somatostatin (SS) 1-28 and SS 1-14 at the C terminus. Little is known about the N-terminal part of pro-SS. In previous studies, using a radioimmunoassay against pro-SS 20-36 (sequence deduced from human cDNA sequence) we have identified a peptide with a molecular mass of approximately 8000 daltons in extracts of pancreas and intestinal mucosa. Using a variety of chromatographic procedures we have now isolated this peptide from extracts of pancreas and intestinal mucosa from pigs. The isolated peptides were sequenced on an Applied Biosystems gas phase sequenator and cleaved with the Asp-N endopeptidase for sequencing of C-terminal fragments. The peptides had an amino acid sequence identical to human pro-SS 1-64. In effluent from isolated perfused preparations of porcine small intestine and pancreas we identified upon appropriate stimulation pro-SS 20-36 immunoreactive peptides that by isocratic high pressure liquid chromatography appeared identical to pro-SS 1-64. An identical peptide was identified in pig plasma. Thus, in pancreas and gut pro-SS processing gives rise to the same pro-SS 1-64 molecule in spite of differential processing of the C terminus (SS 1-14 in pancreas and SS 1-28 in gut). The eventual hormonal role of pro-SS 1-64 may now be evaluated.
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PMID:Prosomatostatin 1-64 is a major product of somatostatin gene expression in pancreas and gut. 256 92

A novel 28-residue somatostatin (SS) has been isolated from anglerfish pancreatic islets and characterized by complete Edman degradation, peptide mapping, and amino acid analysis. The primary structure of this anglerfish SS-28 (aSS-28) containing hydroxylysine (Hyl) was established to be H-Ser-Val-Asp-Ser-Thr-Asn-Asn-Leu-Pro-Pro-Arg-Glu-Arg-Lys-Ala-Gly-Cys- Lys-Asn-Phe-Tyr-Trp-Hyl-Gly-Phe-Thr-Ser-Cys-OH. This sequence (with the exception of hydroxylysine-23, which is replaced by lysine) is identical to the sequence of the COOH-terminal 28 residues of prepro-SS II predicted on the basis of cDNA analysis [Hobart, P., Crawford, R., Shen, L., Pictet, R. & Rutter, W. J. (1980) Nature (London) 288, 137-141]. This is the first instance in which hydroxylysine (to date characteristically observed in collagen or collagen-like structures) has been found in a potential regulatory peptide. Chromatographic characterization of peptides, radiolabeled in islet culture, revealed that aSS-28 contained 10-12% of the radioactivity incorporated into the 8000- to 1000-dalton SS-like polypeptides, whereas 88-90% of this radioactivity was detected in anglerfish SS-14. It appears probable that aSS-28 represents the predominant primary cleavage product derived from prepro-SS II by cleavage at the COOH-terminal side of a single arginine. Based on knowledge of the collagen biosynthesis, it is speculated that hydroxylation may take place as an early post-translational event.
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PMID:Processing of an anglerfish somatostatin precursor to a hydroxylysine-containing somatostatin 28. 285 89

It has been predicted on the basis of cDNA sequence analysis that anglerfish pancreatic islets contain at least two different preprosomatostatins (I and II). The C-terminal amino acid sequences of preprosomatostatin I and II were predicted to be identical to mammalian hypothalamic somatostatin-14 (SS-14) and its analog [Tyr7, Gly10]SS-14, respectively. That SS-14 is expressed in anglerfish pancreatic islets, has been shown earlier in pulse-chase experiments and by chemical characterization. However, it was observed that [Tyr7, Gly10]SS-14 was not expressed as such, but as part of larger polypeptides. Pulse-chase experiments combined with reverse-phase high pressure liquid chromatography, amino acid analysis with two different chromatographic systems, and complete Edman degradation indicated that preprosomatostatin II is processed in anglerfish islets to two different forms of somatostatin-28 (SS-28). The primary structure of the major form containing hydroxylysine (Hyl) was determined to be: H-Ser-Val-Asp-Ser-Thr-Asn-Asn-Leu-Pro-Pro-Arg- Glu-Arg-Lys-Ala-Gly-Cys-Lys-Asn-Phe-Tyr-Trp-Hyl-Gly-Phe-Thr-Ser-Cys-OH. The amino acid sequence of the minor form differs only at residue 23 by substitution of lysine for hydroxylysine. This is the first time that hydroxylysine, an amino acid which characteristically occurs in collagen or collagen-like structures has been identified in a potential regulatory peptide. It can be speculated that this amino acid is formed by post-translational hydroxylation of a lysine C-terminally linked to a glycine residue and thus modified at a site which has been recognized as hydroxylation site in collagen or collagen-like structures. The biological consequences of this unusual modification are being investigated.
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PMID:Anglerfish pancreatic islets produce two forms of somatostatin-28. 286 28

Three different somatostatins have been isolated from the pancreatic islet tissue of the coho salmon (Oncorhynchus kisutch) by gel filtration and HPLC. Two of these peptides contain 14 amino acids and the larger third peptide consists of 25 amino acids. The sequence of the salmon SST-25 is Ser-Val-Asp-Asn-Leu-Pro-Pro-Arg-Glu-Arg-Lys-Ala-Gly -Cys-Lys-Asn-Phe-Tyr-Trp-Lys-Gly-Phe-Thr-Ser-Cys. The sequence of the salmon SST-14-I is Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys. The other small somatostatin (SST-14-II) which was not sequenced has an amino acid composition identical to the C-terminal 14 amino acids of the SST-25 and it is probably derived from this larger form. Evidence for low levels of a somatostatin containing 28 amino acids is also presented. This SST-28 appears to be an N-terminal extended precursor of SST-25 or a peptide derived via alternative processing of a common preprosomatostatin. Injected into juvenile salmon, SST-25 caused a decline in circulating levels of plasma insulin, depletion of liver glycogen, and activation of lipolytic pathways. Juvenile salmon treated with anti-SST-25 serum revealed elevated levels of plasma insulin as well as an increase of the glycogen content of the liver.
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PMID:Characterization of coho salmon (Oncorhynchus kisutch) islet somatostatins. 287 19

We recently identified carboxyl-terminally extended progastrin posttranslational processing intermediates in G cells of the gastric antrum and demonstrated that they are cosecreted with gastrin. To determine the physiological significance of these intermediates, we examined the biological activity of two synthetic gastrin precursor analogues that correspond to hexagastrin with carboxyl-terminal extensions, Tyr-Gly-Trp-Met-Asp-Phe-Gly (GL-7) and Tyr-Gly-Trp-Met-Asp-Phe-Gly-Arg-Arg (GL-9) on gastric parietal and D cells isolated from canine fundic mucosa. Both analogues were as efficacious as gastrin heptadecapeptide in displacing 125I-[Leu15]gastrin from binding sites on the two cell types and in stimulating [14C]aminopyrine uptake by parietal cells and somatostatin release from D cells. However, both analogues were 10(4)- to 10(5)-fold less potent than gastrin heptadecapeptide in these activities. Our results indicate that progastrin processing intermediates do not have physiologically relevant actions under normal circumstances and support the notion that carboxyl-terminally amidated peptides such as gastrin require the amide moiety for biological activity.
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PMID:Biological activity of progastrin posttranslational processing intermediates. 288 87

The products and an intermediate of preprosomatostatin-II processing in the anglerfish islet were purified and subjected to structural analysis. The peptides isolated identify the site of signal cleavage (between Ser-24 and Gln-25). The prohormone is further processed at Arg-97 and, to a lesser extent, at the two adjacent basic amino acid residues Lys-61 and Arg-62. A 28-residue somatostatin is also generated which can be hydroxylated at Lys-23. A proteolytic processing site which would form the 14-residue somatostatin does not appear to be used to a significant degree. Fast atom bombardment mass spectrometry (FABMS) was used to demonstrate that the amino-terminal residues of peptides 25-60, and 25-90 are pyroglutamic acid, a modification which precludes Edman degradation of these peptides. Analysis of the peptides and tryptic peptide maps by FABMS allowed confirmation of the sites of prohormone conversion and indicated that terminal basic residues were removed during processing. Three amino acid residues were also found to differ from the amino acid sequence deduced from the cDNA and were localized to specific regions by FABMS analysis. Residues found to differ from the cDNA (cDNA in parentheses) were: Asp-77 (Thr), Val-78 (Phe), and Gly-90 (Glu). Mass assignments were confirmed by running a single cycle of Edman degradation prior to FABMS. The peptides noted above were also examined by Edman sequence analysis. The sequence of a cDNA clone to preprosomatostatin-II was re-examined in light of the observed differences at the protein level. This study emphasizes the utility of FABMS in prohormone processing studies and in identification of post-translational processing events.
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PMID:Post-translational processing of preprosomatostatin-II examined using fast atom bombardment mass spectrometry. 288 72

Cleavage of the peptide bonds of preprosomatostatin at basic residues near the carboxyl terminus yields somatostatin-14, somatostatin-28, and somatostatin-28 (1-12). However, little is known about the molecular forms derived from the amino terminal portion of the precursor, even though this part of the prohormone is highly conserved through evolution. By using an antibody against the amino terminus of prosomatostatin, a decapeptide with the structure Ala-Pro-Ser-Asp-Pro-Arg-Leu-Arg-Gln-Phe, corresponding to preprosomatostatin (25-34), was isolated from the endocrine portion of the rat stomach, the gastric antrum. The antral decapeptide may represent a bioactive product generated from prosomatostatin after a monobasic cleavage similar to that involved in the formation of somatostatin-28. In fact, a monobasic cleavage requires two basic residues and a domain containing nonpolar amino acids such as alanine or leucine, or both.
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PMID:A new prosomatostatin-derived peptide reveals a pattern for prohormone cleavage at monobasic sites. 289 Nov 88

The cyclostomes represent the first class of vertebrate in evolution to develop an endocrine pancreas. Two peptides with somatostatin-like immunoreactivity were isolated from the islet organ of one such cyclostome, the Atlantic hagfish (Myxine glutinosa). The primary structure of the more abundant peptide was established as: Ala-Val-Glu-Arg-Pro5-Arg-Gln-Asp-Gly-Gln10-Val-His-Glu-Pro- Pro15-Gly-Arg-Glu-Arg-Lys20-Ala-Gly-Cys-Lys-Asn25-Phe- Phe-Trp-Lys-Thr30-Phe-Thr-Ser-Cys. The second peptide, comprising 27% of the total immunoreactivity in the islet extract, was identical to mammalian somatostatin-14. The pathway of posttranslational processing of prosomatostatin in the hagfish islet differs markedly from the pathway in the higher vertebrates. In the mammalian pancreas, prosomatostatin is cleaved at the site of the single arginyl residue (corresponding to position 6 in hagfish somatostatin-34) and at the arginine-lysine site (corresponding to positions 19 and 20 in the hagfish peptide) to generate somatostatin-14 and somatostatin-28(1-12)-peptide. In the hagfish islet, Arg6 is not used as a cleavage site and cleavage at Arg19-Lys20 represents only a minor pathway of processing. The data provide further evidence of the strong evolutionary pressure to conserve the complete amino acid sequence of somatostatin-14.
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PMID:Primary structures of somatostatins from the islet organ of the hagfish suggest an anomalous pathway of posttranslational processing of prosomatostatin-1. 289 18


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