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)

The effects of the native somatostatin-14 (SST-14) and of its analog octreotide (OCT) on the activity of protein tyrosine kinases (PTK) in the normal rat anterior pituitary gland, diethylstilbestrol (DES)-induced rat pituitary tumor and murine colonic cancer Colon 38 were studied in vitro. PTK activity was estimated in tissue homogenates using gamma-[32P]ATP and poly (Glu80, Tyr20) as a substrate. It was found that both SST-14 and OCT suppressed the PTK activity in all examined tissues. The suppressive effect was more pronounced in DES-induced pituitary tumor than in normal anterior pituitary gland, and in the former, OCT was more effective than SST-14. In contrast, SST-14 stronger suppressed PTK activity in colonic cancer than OCT. We hypothesize that SST-14 acts on PTK activity in colonic cancer mainly via SSTR-1 subtype of somatostatin receptors.
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PMID:Differential effects of somatostatin and its analog on protein tyrosine kinases activity in the rat pituitary and the murine colonic tumors. 961 Mar 66

[Tyr0]-somatostatin-14 (SST-14) was converted to the corresponding radiolabeled 125I-[Tyr0]-SST-14 derivative by use of the chloramine-T technique. After solid-phase extraction (SPE) of the crude radiopeptide with microfine silica gel and desorption with acetone-water-acetic acid 39:40:1, the label was subjected to size exclusion chromatography (SEC) on Sephadex G-25 fine. Fractions attributable to the target compound were collected and investigated with respect to their specific as well as non-specific binding to a specific anti-somatostatin antibody. All fractions exhibiting an optimum ratio of specific versus non-specific binding were pooled and lyophilized for their further use in both radioimmunoassay (RIA) measurements of somatostatin like immunoreactivity (SLI) and receptor-binding experiments. A specific activity of approx. 1.6 x 10(6) Ci/M was calculated for the radiolabel prepared in this manner. Approximately 85-90% of radioactivity attributable to labeled [Tyr0]-SST species was incorporated into the desired mono-iodinated component. When 125I-[Tyr0]-SST-14 was purified by reversed-phase high performance liquid chromatography (RP-HPLC) using isocratic elution with 0.1 M triethylammonium formate (TEAF) buffer of pH 2.2 in 22% acetonitrile after prior SPE, specific binding decreases to about 80% compared with the value obtained for the radiopeptide subjected to SEC. Nevertheless, RP-HPLC proves as an efficient tool for rapid purity control of 125I-[Tyr0]-somatostatin-14 samples at different storage time intervals.
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PMID:Preparation and chromatographic purification of 125I-[Tyr0]-somatostatin-14 for the use in radioimmunoassay and receptor-binding experiments. 971 Aug 95

KET is a member of the newly discovered family of proteins that is related to the tumor suppressor p53. Here we describe the molecular cloning of a human cDNA of 4846 bp encoding a protein of 680 amino acids. The human KET protein shares 98% identity with the previously characterized rat homolog. The remarkably high degree of conservation lends support to the notion that KET proteins have important basic functions in development and differentiation. Using the GeneBridge 4 radiation hybrid panel, we have mapped KET to human Chromosome (Chr) 3q27. KET is located between the somatostatin gene SST (proximal) and the apolipoprotein D gene APOD (distal) in a region of conserved synteny to mouse Chr 16. This chromosomal region is deleted in early stages of tumorigenesis of mouse islet cell carcinomas and contains the hitherto unidentified Loh2 gene, a putative suppressor of angiogenesis. The murine homolog Ket was mapped in an interspecific backcross panel and falls into this region of loss of heterozygosity. From our mapping data we infer that KET might act as a tumor suppressor and is considered as a candidate for Loh2.
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PMID:Cloning and chromosomal mapping of the human p53-related KET gene to chromosome 3q27 and its murine homolog Ket to mouse chromosome 16. 979 41

1. Neurogenic plasma extravasation evoked by topical application of 1% vv(-1) mustard oil on the skin of the acutely denervated rat hindleg (primary reaction) inhibited the development of a subsequent oil-induced plasma extravasation induced in the skin of the contralateral hindleg by 49.3+/-7.06% (n=9) and in the conjunctival mucosa due to 0.1% wv(-1) capsaicin instillation by 33.5+/-10.05% (n=6). The primary reaction also inhibited the non-neurogenic hindpaw oedema evoked by s.c. injection of 5% wv(-1) dextran into the chronically denervated hindpaw by 48.0+/-4.6% (n= 5). 2. Capsaicin injection (100 microg ml(-1) in 50 microl, s.c.) into the acutely denervated hindleg caused 56.5+/-4.0% (n=5) inhibition in the intensity of plasma extravasation elicited by 1% vv(-1) mustard oil smearing on the contralateral side. After chronic denervation, subplantar injection of 5% wv(-1) dextran elicited a non-neurogenic inflammatory response with intensive tissue oedema without causing any systemic anti-inflammatory effect. Bilateral adrenalectomy did not inhibit the mustard oil-induced anti-inflammatory effect in the contralateral hindleg. 3. Pretreating the rats with polyclonal somatostatin antiserum (0.5 ml rat(-1), i.v.) or with the somatostatin depleting agent cysteamine (280 mg kg(-1), s.c.) prevented the inhibitory action of mustard oil-induced inflammation on subsequent neurogenic plasma extravasation and strongly diminished the inhibition of non-neurogenic oedema formation evoked by dextran. 4. Exogenous somatostatin (10 microg kg(-1), i.p.) caused a 30.3+/-8.3% (n=6) inhibition of plasma extravasation caused by mustard oil smearing on the acutely denervated hindleg and this inhibitory effect was abolished by somatostatin antiserum (0.5 ml rat(-1), i.v.). The plasma level of somatostatin-like immunoreactivity (SST-LI) increased by 40.03+/-6.8% (n= 6) 10 min after topical application of 1% vv(-1) mustard oil on the acutely denervated hindpaws compared to the paraffin oil treated control group. Chronic denervation of the hindlegs or cysteamine (280 mg kg(-1), s.c.) pretreatment prevented the mustard oil-induced elevation of SST-LI in plasma. 5. It is concluded that chemical excitation of the capsaicin-sensitive sensory receptors not only induces local neurogenic plasma extravasation but also inhibits the development of a subsequent inflammatory reaction at remote sites of the body in the rat. A role for somatostatin in this systemic anti-inflammatory effect is suggested.
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PMID:Systemic anti-inflammatory effect induced by counter-irritation through a local release of somatostatin from nociceptors. 983 33

The cellular composition and topography of the pancreatic islet of Oreochromis niloticus, now known to be a donor source for islet xenotransplantation studies, were characterized. Whole tilapia islets were harvested using an enzymatic method and then further digested into single-cell preparations. Cell cytospin preparations of islet cells and paraffin sections of whole islets were stained using antisera against tilapia insulin, human glucagon, salmon somatostatin-25 (SST-25), human somatostatin-14 (SST-14), and salmon peptide tyrosine-tyrosine (PYY) using the immunoperoxidase method. Cell counts, performed on cytospin preparations using a Quantimet 570 computerized image analysis system, revealed that O. niloticus islets contained 78% endocrine cells and 22% immunonegative cells (i. e., mainly nucleated erythrocytes and rare tissue eosinophils). The proportions of immunopositive endocrine cell types were: 42.3% insulin immunopositive cells, 11.5% glucagon immunopositive cells, 23.1% SST-25 immunopositive cells, 21.8% SST-14 immunopositive cells, and 1.3% PYY immunopositive cells. Islet cell topography was evaluated using histologic sections of whole endocrine pancreata including large, medium, and small islets. Round to polygonal insulin immunopositive cells with round central nuclei were distributed in clusters throughout both the principal and the smaller islets. Elongate SST-14 immunopositive cells were closely associated with the clusters of insulin immunopositive cells; both were surrounded by SST-25 immunopositive cells, which were similar in shape to the insulin immunopositive cells. There were elongate glucagon immunopositive cells throughout the islets, whereas the PYY immunopositive cells were restricted to the periphery and to channels of fibrovascular connective tissue penetrating the islets.
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PMID:Immunocytochemical characterization of the pancreatic islet cells of the Nile Tilapia (Oreochromis niloticus). 1009 58

Somatostatin and its analogs are active in the inhibition of SST receptor-positive endocrine neoplasms, but their activity and mechanism in nonendocrine tumors is not clear. Somatostatin potently inhibited growth of a Kaposi's sarcoma xenograft in nude mice, yet in vitro the tumor cells did not express any known somatostatin receptors and were not growth inhibited by somatostatin. Histological examination revealed limited vascularization in the somatostatin-treated tumors as compared with the controls. Somatostatin was a potent inhibitor of angiogenesis in an in vivo assay. In vitro, somatostatin inhibited endothelial cell growth and invasion. Migration of monocytes, important mediators of the angiogenic cascade, was also inhibited by somatostatin. Both cells types expressed somatostatin receptor mRNAs. These data demonstrate that somatostatin is a potent antitumor angiogenesis compound directly affecting both endothelial and monocytic cells. The debated function of somatostatin in tumor treatment and the design of therapeutic protocols should be reexamined considering these data.
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PMID:Somatostatin controls Kaposi's sarcoma tumor growth through inhibition of angiogenesis. 1009 25

In mammals, somatostatin seems to be involved in the control of ovarian steroidogenesis. There have been no studies on the presence or actions of somatostatin in the ovary of nonmammalian vertebrates. The localisation of somatostatin-14 was examined immunohistochemically using the antibody to somatostatin-14 in the ovary of the African lungfish Protopterus annectens. Immunoreactivity was present in the granulosa cells of mature ovarian follicle examined by light microscopy. Using an oligonucleotide probe complementary to mRNA for somatostatin-14 and labelled at the 3'-end with alpha-35S, in situ hybridisation demonstrated somatostatin-14 mRNA distributed in cells showing the same localisation as that of the immunoreactive cells. Binding sites for SST-14 were identified with autoradiography using [125I]somatostatin-14. Binding sites were localised on granulosa and theca cells. Somatostatin-14 may be thus synthesised in the lungfish ovary.
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PMID:Somatostatin in the ovary of an African lungfish (Protopterus annectens): an in situ hybridisation, immunohistochemical, and autoradiographical study. 1020 77

In this study, we have used the mouse intestine and the Ussing short circuit technique to compare the effects and mechanism of action of somatostatin (SST, 0.1 microM) on cAMP- and Ca(2+)-mediated ion secretion in the duodenum and colon of the Swiss-Webster mouse. The cAMP-dependent secretagogues, prostaglandin E(2) (1 microM) and dibutyryl-cAMP (150 microM) increased short circuit current (I(sc)) in both regions, but only the colonic response was inhibited by SST. This inhibition was independent of enteric nerves, suggesting a direct action on the epithelial cells. The Ca(2+)-dependent secretagogue carbachol (10 microM) stimulated a transient increase in I(sc) in both intestinal segments. In the duodenum, SST partially inhibited this increase in I(sc) and both the responses to carbachol and SST were independent of enteric nerves. In the colon, while SST inhibited the carbachol induced increase in I(sc), pre-treatment with tetrodotoxin (750 nM) profoundly inhibited the carbachol induced increase in I(sc), thus markedly reducing the inhibitory effect of SST. This indicates an involvement of the enteric nervous system in the response to carbachol and the action of SST in the colon. These data indicate marked regional differences within the mouse intestine of the effects of SST on ion secretion and demonstrate different mechanisms of action of SST in the duodenum and colon.
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PMID:Effect of somatostatin on electrogenic ion transport in the duodenum and colon of the mouse, Mus domesticus. 1084 Feb 21

To investigate the effects of somatostatin (somatotropin release-inhibiting factor, SRIF) on the regulation of SST(2A) receptors in mammalian brain, we examined how blockade of SRIF release or stimulation by the SRIF analog [d-Trp(8)]-SRIF would affect the expression and cell surface availability of SST(2A) receptors in rat brain slices. First, we measured the intensity of SST(2A) immunoreactivity, using quantitative light microscopic immunocytochemistry, and levels of SST(2A) mRNA, using semiquantitative RT-PCR, under conditions of acute SRIF release blockade. Incubation of slices from the claustrum or basolateral amygdala, two regions previously shown to contain high concentrations of SST(2A) receptors, in Ca(2+)-free Ringer's for 40 min induced a decrease in the intensity of SST(2A) receptor immunoreactivity and concentration of SST(2A) mRNA as compared with control values obtained in Ca(2+)-supplemented Ringer's. These effects were counteracted in a dose-dependent manner by the addition of 10-100 nm [d-Trp(8)]-SRIF to the Ca(2+)-free medium. Furthermore, both of these effects were abolished in the presence of the endocytosis inhibitors phenylarsine oxide or hyperosmolar sucrose, suggesting that they were dependent on receptor internalization. Electron microscopic immunogold labeling confirmed the existence of an agonist-induced internalization of SST(2A) receptors in central neurons. At a high (10 microm), but not at a low (10 nm), concentration of agonist this internalization resulted in a significant decrease in cell surface receptor density, irrespective of the presence of Ca(2+) in the medium. Taken together, these results suggest that ligand-induced endocytosis is responsible for rapid transcriptional (increase in SST(2A) expression) and trafficking (loss of cell surface receptors) events involved in the control of the somatostatinergic signal.
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PMID:Somatostatin-induced regulation of SST(2A) receptor expression and cellsurface availability in central neurons: role of receptor internalization. 1093 40

A new line (FP) of human foetal lung fibroblasts was analysed for the expression of functional, G-protein coupled somatostatin receptors (SSTR). By means of RT-PCR, we identified the expression of SSTR1, SSTR2, SSTR3 and SSTR4, but not SSTR5, subtypes. The same technical approach evidenced the expression of stimulatory (alphas) and inhibitory (alphai1, alphai2 and alphai3) G-protein subunits. The functionality of SSTR was established from the observation of a dose-dependent inhibitory role of SST upon isoproterenol-stimulated adenylyl cyclase activity, an effect that involves G-protein action. Moreover, the functionality of G-proteins was assessed by means of experiments with forskolin and a nonhydrolysable GTP analogue that showed either Gi or Gs activation in the regulation of adenylyl cyclase. Present results represent a first pharmacological characterization of this new line of human foetal lung fibroblasts. The selective presence of some SSTR subtypes and G-protein subunits in addition to the regulatory network of the adenylyl cyclase pathway are features of recognized involvement in cell growth mechanisms. It is of interest for a cell class widely used to study this topic but also important in lung physiology and pathophysiology.
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PMID:Identification of functional somatostatin receptors and G-proteins in a new line of human foetal lung fibroblasts. 1101 9


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