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)

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

The somatostatin analogs D-Phe-Cys-D-Trp-Lys-Thr-Cys-Thr and the corresponding penicillamine compounds have been prepared and tested for their ability to displace [3H]naloxone and [3H] [D-Ala2, D-Leu5]enkephalin from rat brain receptors. While somatostatin and the cystine containing peptide displayed little or no preference for either receptor system, the substitution of penicillamine at position two or seven resulted in analogs that displayed opposite receptor selectivity. The substitution of tyrosine for phenylalanine at position three resulted in a large increase in opiate receptor affinity which may be related to the known requirement for a phenolic hydroxyl moiety in the rigid opiate and enkephalin systems. Conformational properties of these analogs were also examined and related to their affinity for opiate and somatostatin receptors in the rat brain.
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PMID:Somatostatin analogs with affinity for opiate receptors in rat brain binding assay. 286 80

Somatostatin-like immunoreactivity (SLI) was purified from frog brain and retina, and the structure of the brain peptide was determined. Frog brain (101 g) and retinal (45 g) tissues were extracted with 3% acetic acid, yielding 9.6 and 0.44 nmol of SLI, respectively. SLI was further purified by chromatography on a somatostatin immunoaffinity column followed by sequential application to reverse-phase C-18 HPLC columns. The brain and retinal peptides, purified roughly 100,000-fold with net yields of 7.5 and 2.3%, respectively, appeared identical in the final steps of purification. The amino acid sequence of brain SLI, as determined by a gas-phase automated Edman degradation technique, was as follows: Ala-Gly-(Cys)-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-(Cys). Our data indicate that despite structural variations in somatostatins of other lower vertebrates, the amino acid sequence of frog brain and, by deduction, retinal SLI is identical to that of somatostatin tetradecapeptide. These findings support the physiological relevance of studies directed at elucidating the neurotransmitter function of somatostatin using the well-established models of frog brain and retina.
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PMID:Purification of somatostatin from frog brain: coisolation with retinal somatostatin-like immunoreactivity. 286 37

Studies were performed to determine whether the cyclic hexapeptide analog of somatostatin, cyclo(N-Me-Ala-Tyr-D-Trp-Lys-Val-Phe) II, could alter circulating levels of neurotensin (NT) and inhibit the release of NT from small intestine following the intraluminal perfusion of lipid and ETOH. The small intestine of anesthetized rats was perfused with 0.9% NaCl, 1mM ETOH, 100 mM ETOH or 1 mM oleic acid with and without the intravenous infusion of the somatostatin analog. Plasma samples collected from the superior mesenteric vein were extracted, chromatographed on HPLC and assayed with both C-terminal and N-terminal antisera to NT. The basal circulating levels of chromatographically and immunochemically identified NT observed during the perfusion of the small intestine with 0.9% NaCl were significantly lower (p less than 0.01) during the IV infusion of the somatostatin analog as compared to animals infused IV with saline. The 2-3 fold increase in plasma levels of NT observed with the intestinal perfusion of oleic acid and ETOH did not occur in animals simultaneously infused IV with the somatostatin analog. The somatostatin analog was also effective in decreasing the basal levels of NT metabolite NT(1-8) as well as inhibiting the increase in this metabolite that accompanies the stimulated release of NT.
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PMID:Inhibition of neurotensin release by a cyclic hexapeptide analog of somatostatin. 286 26

The effect of somatostatin (SRIH) on the release of growth hormone (GH) induced by lysine-vasopressin (LVP) was studied in six normal subjects. They were injected intravenously with 0.06 I. U./kg of LVP alone or in combination with SRIH (an intravenous bolus of 100 micrograms 10 minutes before LVP injection, followed by the constant infusion of 500 micrograms over 90 minutes). LVP strikingly increased serum concentrations of GH; this response was significantly reduced by the treatment with SRIH. This finding provides evidence that the effect of LVP on serum GH levels is sensitive to the inhibition by SRIH; it is proposed that the stimulating action of LVP on GH secretion might be mediated by the inhibition of endogenous SRIH.
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PMID:Inhibition by somatostatin of the release of growth hormone induced by lysine-vasopressin in normal subjects. 286 93

In previous work, radioimmunoassay was used to document the presence of somatostatin-like immunoreactive material in the rabbit retina. The present study was undertaken to determine the cellular localization of that material by light microscopic immunocytochemistry. Rabbit retinas were fixed by immersion in paraformaldehyde-lysine-periodate and reacted, either as whole retinas or as 50 microns Vibratome cross-sections, with an antiserum directed against somatostatin-14. Consistent staining of neuronal perikarya was seen only in the retinas of rabbits that had been pretreated with intravitreal injections of colchicine. Specifically stained cell bodies are present in the ganglion cell layer; the cells give rise to fibers in both the innermost and outermost sublaminas of the inner plexiform layer. In retinal whole mounts, the cells possess two or three primary dendrites with sparse branching. The dendritic fields are up to 1 mm in diameter, and adjacent dendritic fields overlap. Many cells have a thin varicose process arising from the soma or a proximal primary dendrite; these processes branch repeatedly within the retina and resemble intraretinal axons. The somatostatin-reactive cells may be associational ganglion cells or displaced amacrine cells; it is less likely that they are ganglion cells with axons projecting to the brain.
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PMID:Somatostatin immunocytochemistry in the rabbit retina. 286 4

In the search for selective and long-acting analogs of somatostatin, nearly 200 compounds were synthesized by solid-phase methods, purified, and tested biologically. Among these octapeptides, some contained N-terminal (Formula: see text) were 177 times and 113 times more potent, respectively, than somatostatin in tests for inhibition of growth hormone release. These two octapeptides containing tyrosine and valine in positions 3 and 6, respectively, were more active and more selective than their Phe-3 and Thr-6 counterparts, D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 and D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Trp-NH2. D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 was also about 6 times more potent than its L-Trp-4 diastereoisomer. The analogs D-Phe-Cys-Tyr-Lys-Val-Cys-Thr-NH2 and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 showed a prolonged duration of action and were able to inhibit growth hormone release for at least 3 hr. Analogs of both Phe-3/Thr-6 and Tyr-3/Val-6 classes also suppressed the release of insulin and glucagon in rats and pentagastrin-induced secretion of gastric acid in dogs, but their potencies in these tests were much smaller than the growth-hormone-release inhibitory activity. Some of these analogs possessed antitumor activities as shown by the inhibition of growth of animal models of prostate, mammary, and ductal pancreatic tumors.
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PMID:Synthesis and biological activity of highly potent octapeptide analogs of somatostatin. 286 90

Differentiation of the respiratory region of fetal mouse lungs was investigated in serum-free medium supplemented with growth factors and hormones. Terminal buds from the margins of a lobe were removed from 16-day fetuses and organ cultures prepared either in submersion culture or at the air-medium interface. It was found that glycyl-L-histidyl-L-lysine, transferrin, and somatostatin were sufficient to promote branching in the absence of serum. However, type II pneumocytes containing lamellar bodies formed only in the presence of thyroxine or dexamethasone. At concentrations of these hormones slightly above the physiological range most of the cells became cuboidal and contained lamellar bodies; at lower concentrations regions of flattened cells appeared. In submersion culture a large, central cavity surrounded by saccules was formed rather than a branched tree. Thus, the pattern of differentiation is significantly influenced by culture conditions.
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PMID:The effect of culture conditions on cytodifferentiation of fetal mouse lung respiratory passageways. 286 41

The effects of somatostatin on fasting and absorptive plasma ammonia and amino acids were studied in 12 cirrhotic patients. They received a 6 h intravenous infusion of somatostatin (500 micrograms/h) or saline, starting 90 min before protein feeding. During the fasting period somatostatin significantly reduced plasma ammonia (-18%) and total tryptophan (-39%), increased plasma leucine (+19%), isoleucine (+17%), glutamine (+22%), glycine (+13%), arginine (+14%) and lysine (+12%), and prevented the significant fall of phenylalanine (-8%), tyrosine (-6%), alanine (-8%) and threonine (-9%) seen with saline. The percent changes in ammonia and glutamine concentrations were inversely correlated (r = -80; p less than 0.001) After protein ingestion, somatostatin slowed the maximal plasma increase in ammonia and alpha-nitrogens by at least two hours, but their total 5 h plasma response was not reduced, and even, in some instances, significantly increased (valine, leucine, glutamine, alanine and serine) with respect to saline. The results suggest that in fasting cirrhotics somatostatin reduces plasma ammonia, probably through an impaired intestinal ammoniogenesis from circulating precursors, and inhibits the disposal of branched chain, aromatic (except tryptophan) and gluconeogenic amino acids. Furthermore, it delays, but does not reduce, the plasma increase in nitrogen after protein ingestion.
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PMID:Effects of somatostatin on plasma ammonia and amino acid profile during fasting and after protein feeding in cirrhotic patients. 287 93

Primary cultures of rat hepatocytes were used for assaying several drugs not previously known for inhibiting the transport of phalloidin. In order to have 50% inhibition (IC50) of the entrance of a tritiated phallotoxin derivative ([3H]demethylphalloin, 1 microM) from the medium into the cells the following concentrations (microM) of the various inhibitors were determined: cyclolinopeptide (0.5), Nocloprost (5.0), Nileprost (7.0), beta-estradiol (42), Verapamil (70). For comparison, the corresponding IC50 values of some known antagonists of phalloidin toxicity were determined by the same method. Moreover, we studied several natural and synthetic phallotoxins and alpha-amanitin for their ability to displace [3H]demethylphalloin from the transporting system. Lineweaver-Burk plots made it obvious that two groups of inhibitors exist. Competitive inhibitors are, for example, antamanide, beta-estradiol, silybin, Nileprost, taurocholate, and the cyclic somatostatin analog cyclo[Phe-Thr-Lys-Trp-Phe-D-Pro], whereas Verapamil and monensin inhibit phallotoxin uptake in a non-competitive way. Considering the very different chemical features of the competitive inhibitors, we tentatively conclude that the phallotoxin transport system selects compounds not on the basis of their chemical features, but rather their physical properties. The physical properties of a typical substrate are low molecular mass, lipophilic nature, and, possibly the presence of rigid ring structures. Negative charges accelerate the transport of a substrate, while positive charges have the opposite effect. The phalloidin-transporting system may represent part of a hepatic equipment which clears portal blood from, for example, bile acids, lipophilic hormones, or xenobiotics. By chance, the transporting system incorporates phallotoxins into the hepatocytes leading to the death of these cells.
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PMID:Characterization of a transporting system in rat hepatocytes. Studies with competitive and non-competitive inhibitors of phalloidin transport. 287 38


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