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)

Antisera raised against various synthetic peptide fragments of the pro-somatostatin molecule were used to visualize immunohistochemically the distributions of different pro-somatostatin fragments in the hypothalamus and posterior pituitary of the Mongolian gerbil. To define the nature of the immunoreactive somatostatin-related molecular forms, gel chromatography combined with radioimmunoassays of hypothalamic and posterior pituitary extracts was performed. Within the hypothalamus, only trace amounts of somatostatin-28 and somatostatin-28(1-12) were present, whereas pro-somatostatin(1-76), pro-somatostatin(1-64), and somatostatin-14 peptides were present in equimolar amounts. In contrast, the posterior pituitary lobe contained equal amounts of somatostatin-14, somatostatin-28, and somatostatin-28(1-12) but no pro-somatostatin(1-76), indicating that pro-somatostatin is further processed during the axonal flow to posterior pituitary nerve terminals. The gel chromatographic data were further substantiated by immunohistochemical data. Thus, perikarya containing all of these five immunoreactivities were strictly confined to the periventricular area and parvocellular subset of the paraventricular nucleus. However, the number of somatostatin-28- and somatostatin-28(1-12)-immunoreactive perikarya was approximately 20% of the number of somatostatin-14- and pro-somatostatin(1-64)-immunoreactive cells. In other hypothalamic areas only somatostatin-14 and pro-somatostatin(1-64) immunoreactivities were detectable in cell bodies. These cell bodies were encountered in the organum vasculosum laminae terminalis; the suprachiasmatic, ventromedial, arcuate, perifornical, and posterior hypothalamic nuclei; and the median preoptic and retrochiasmatic areas. In situ hybridization histochemistry revealed that the cellular distribution of pro-somatostatin mRNA corresponds to that of somatostatin-14 and pro-somatostatin immunoreactivity, suggesting that the immunoreactive material observed within the cell bodies is synthetized there and that the differences in density of immunoreactivities may be explained by intracellular processing of pro-somatostatin. Somatostatinergic nerve fibers and terminals in hypothalamic areas and the posterior pituitary lobe were immunoreactive to all of the employed antisera. From the present results, obvious differences between intrahypothalamic and hypothalamo-pituitary somatostatinergic neurons emerge. Within hypothalamic neurons not projecting to the median eminence and the posterior pituitary lobe, pro-somatostatin is posttranslationally processed in the cell body predominantly into pro-somatostatin(1-64) and somatostatin-14. Otherwise, within periventricular neurons projecting to the median eminence and the posterior pituitary lobe, pro-somatostatin is posttranslationally processed during the axonal flow into pro-somatostatin(1-64), somatostatin-14, somatostatin-28, and somatostatin-28(1-12).
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PMID:Distribution and characterization of different molecular products of pro-somatostatin in the hypothalamus and posterior pituitary lobe of the Mongolian gerbil (Meriones unguiculatus). 134 64

Somatostatin (SRIF) receptors are coupled to the catalytic subunit of adenylyl cyclase via pertussis toxin-sensitive guanine nucleotide-binding regulatory proteins (G proteins). To identify which G proteins link SRIF receptors to adenylyl cyclase, G(o) alpha, Gi alpha, and its different subtypes were individually blocked in AtT-20 cell membranes with G alpha subtype-selective antisera. Antiserum directed against the carboxyl-terminal region of Gi alpha blocked SRIF inhibition of forskolin-stimulated adenylyl cyclase activity, and this effect was prevented by the peptide to which the antiserum was generated. However, antiserum directed against the carboxyl-terminal region of G(o) alpha did not affect SRIF inhibition of adenylyl cyclase activity, indicating that Gi alpha couples SRIF receptors to adenylyl cyclase but G(o) alpha does not. Peptide-directed antisera against Gi alpha 1 completely blocked SRIF inhibition of adenylyl cyclase activity. In contrast, antisera directed against either Gi alpha 2 or Gi alpha 3 did not affect the actions of SRIF. The results of these studies indicate that Gi alpha 1 selectively couples SRIF receptors to the catalytic subunit of adenylyl cyclase in AtT-20 cell membranes. Because previous studies have shown that SRIF receptors are able to couple to Gi alpha 1, Gi alpha 3, and G(o) alpha, the results suggest that different G proteins may specify the coupling of SRIF receptors to distinct cellular effector systems.
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PMID:Gi alpha 1 selectively couples somatostatin receptors to adenylyl cyclase in pituitary-derived AtT-20 cells. 134 39

The influence of altered endogenous GH status on somatostatin (somatotropin release-inhibiting hormone; SRIF) gene expression was studied in two transgenic mouse models. Transgenic dwarf mice carried the rat GH gene promoter fused to the diphtheria toxin A-chain gene, placing toxin expression under GH promoter control. As a result, the toxic product of the transgene ablated all GH-expressing cells, resulting in undetectable circulating GH, reduced weight (10.6 +/- 1.0 g for transgenic dwarfs vs. 29.5 +/- 1.7 g for controls; P less than 0.001), and no detectable somatotrophs. Transgenic giant mice contained a construction combining a widely expressed metallothionein promoter and the human GH-releasing hormone (hGHRF) structural gene. Transgene expression of hGHRF resulted in overproduction of endogenous mouse GH in the anterior pituitary and weight increases (42.7 +/- 2.7 g for giants vs. 29.5 +/- 1.7 g for controls; P less than 0.005). Using in situ hybridization, control mice, transgenic dwarfs, and transgenic giants were compared for levels of prepro-SRIF mRNA. Hybridization signal intensities for prepro-SRIF mRNA were similar in transgenic dwarfs to those in littermate nontransgenic mice in non-GH-regulating regions of the brain, such as cortex (control, 31 +/- 2 U; dwarf, 27 +/- 2) and reticulothalamic nucleus (control, 41 +/- 2 U; dwarfs, 39 +/- 3). Transgenic giant mice had hybridization intensity of SRIF mRNA similar to that of normals in cortex (controls, 31 +/- 2 U; giant, 27 +/- 1) and reticulothalamic nucleus (controls, 41 +/- 2 U; giant, 40 +/- 4). In the GH-regulating neurons of the anterior periventricular hypothalamus (PeN), prepro-SRIF mRNA signal in transgenic dwarf mice decreased to 60% of that in controls (88 +/- 13 U for dwarfs vs. 147 +/- 17 U for controls; P less than 0.01), although the numbers of mRNA-expressing cells in the PeN were not different between the transgenic dwarfs and controls (dwarfs, 69 +/- 6 cells; controls, 72 +/- 4 cells). The transgenic giant mice had 230% higher prepro-SRIF mRNA signal than control mice in the PeN (343 +/- 30 U in giants vs. 147 +/- 17 U in controls; P less than 0.001). Again, the numbers of mRNA-expressing cells were not different in giants (57 +/- 9) and normals (72 +/- 4). These results suggest that while the lack of endogenous GH is accompanied by a slight decrease in transcriptional expression of SRIF in the PeN, the overproduction of endogenous GH greatly stimulates hypothalamic SRIF steady state mRNA levels.
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PMID:Hypothalamic preprosomatostatin messenger ribonucleic acid expression in mice transgenic for excess or deficient endogenous growth hormone. 134 38

Exogenous GH is known to exert a negative feedback effect on its own responsiveness to GH-releasing factor (GRF); however, the mechanism is not known. In the present study we examined the time course of effects of a single sc administration of recombinant human (rh) GH on GH responsiveness to GRF and investigated the possible involvement of somatostatin (SRIF) in this response. Free-moving adult male rats were administered 200 micrograms rhGH, sc, at 0800 h and subsequently challenged with 1 microgram GRF-(1-29)NH2, iv, at times of spontaneous peaks (1100 and 1500 h) and troughs (1300 h) in GH secretion during a 6-h (1000-1600 h) sampling period. H2O-injected control rats exhibited the typical cyclic responsiveness to GRF stimulation, with GRF-induced GH release significantly greater during peak compared to trough periods of the GH rhythm. Pretreatment with rhGH 3 h before GRF injection markedly inhibited the GH response to GRF at a peak time [integrated GH release over 30 min, 1135 +/- 271 vs. 6372 +/- 1185 ng/ml.30 min in H2O-injected controls (mean +/- SE); P less than 0.01]. In striking contrast, 5 h after rhGH administration, there was a 6-fold augmentation of GH responsiveness to GRF compared to that in H2O-injected controls at a trough time (7032 +/- 1622 vs. 1128 +/- 216 ng/ml.30 min; P less than 0.01). High GH responsiveness to GRF was preserved 7 h after rhGH injection. Passive immunization of rhGH-treated rats with SRIF antiserum reversed the rhGH-induced blunted GH response at 3 h (7985 +/- 366 vs. 1705 +/- 431 ng/ml.30 min in rhGH-treated control rats given normal sheep serum; P less than 0.01) and completely restored GH responsiveness to levels as high as those in H2O-injected controls. These results demonstrate that 1) a single sc injection of rhGH markedly attenuates GH responsiveness to GRF acutely for about 3 h, but subsequently enhances somatotroph sensitivity to the stimulatory actions of GRF; and 2) the short term blunting of GRF-induced GH release by rhGH is due at least in part to increased release of endogenous SRIF. The subsequent potentiation of GH responsiveness to GRF is probably due to a SRIF-mediated build-up of pituitary GH stores in a readily releasable pool. Such a mechanism of GH autofeedback may play a physiological role in the genesis of pulsatile GH secretion.
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PMID:Time-dependent reduction and potentiation of growth hormone (GH) responsiveness to GH-releasing factor induced by exogenous GH: role for somatostatin. 134 39

This study examines the effects of donor age on exogenous somatostatin inhibition of insulin secretion stimulated by 10 mM D-glyceraldehyde and by 20 mM beta-D-glucose in isolated perfused rat pancreas. Both 6 and 30 nM synthetic somatostatin-14 affect both glyceraldehyde- and glucose-stimulated insulin secretion to a greater degree in pancreases from old animals (24-27 months) than in those from young (2-5 months). We conclude that an increased sensitivity to inhibitory actions of somatostatin during aging, observed in pituitary tissues in vitro, occurs in pancreatic tissues as well and may constitute a general phenomenon in tissues subject to somatostatin inhibition.
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PMID:Aging enhances inhibitory action of somatostatin in rat pancreas. 134 43

The effects of somatostatin-28, somatostatin-14, and a synthetic somatostatin octapeptide analogue, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Nal-NH2 (cyclo SS-8) were examined on contraction of dispersed gastric smooth muscle cells from guinea pigs. The somatostatins did not cause contraction of gastric smooth muscle cells, nor did they inhibit carbachol-stimulated contraction. However, they reversed vasoactive intestinal peptide (VIP)-induced inhibition (relaxation) of carbachol-stimulated contraction. Somatostatin-28 had a half-maximal effect (EC50) at 1.6 +/- 0.8 nM, cyclo SS-8 at 0.6 +/- 0.3 nM, but somatostatin-14 had no effect even when used in concentrations as high as 1 microM. Incubation of muscle cells with peptidase inhibitors phosphoramidon (1 microM) plus amastatin (10 microM) had no effect on the EC50 of somatostatin-28 or cyclo SS-8 but increased the potency of somatostatin-14 greater than 1,000-fold. When peptides were incubated with muscle cells and the products applied to high-performance liquid chromatography, cyclo SS-8 was not degraded, but somatostatin-14 was rapidly degraded when present alone, and the addition of peptidase inhibitors partially inhibited the degradation. Cyclo SS-8 had its maximal effect at 0.5-1 min and inhibited relaxation induced by VIP, isoproterenol, glucagon, or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). Cyclo SS-8 partially inhibited the increase in VIP-stimulated cAMP. Preincubation with pertussis toxin blocked the inhibitory action of cyclo SS-8 on VIP or DBcAMP-induced relaxation. These results indicate that gastric smooth muscle cells rapidly degrade somatostatin-14 and suggest that muscle cell peptidases could have a major effect on the actions of somatostatin-14.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Actions of somatostatins on gastric smooth muscle cells. 134 75

A case of duodenal somatostatinoma is described in a patient with Von Recklinghausen neurofibromatosis. The patient presented with exocrine pancreatic insufficiency, probably due to distal obstruction of the pancreatic duct by the tumor. Preoperative evaluation with calcium-pentagastrin and tolbutamide stimulation tests were nondiagnostic. At laparotomy, local excision of the tumor was performed. Pathological findings were compatible with duodenal somatostatinoma, causing pancreatic fibrosis. Somatostatin extracted from the tumor coeluted with the somatostatin-14 standard on high performance liquid chromatography (HPLC).
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PMID:Exocrine pancreatic insufficiency and pancreatic fibrosis due to duodenal somatostatinoma in a patient with neurofibromatosis. 134 57

Vasoactive intestinal polypeptide (VIP) immunoreactive (IR) neurons in the rabbit retina constitute a population of wide-field amacrine cells. To better define this cell population, we examined the coexpression of VIP with other putative retinal transmitters or their biosynthetic enzymes, including gamma-aminobutryic acid (GABA), tyrosine hydroxylase (TH), and somatostatin (SRIF). Colchicine-treated retinas were immersion fixed in 4% paraformaldehyde. The retinas were cut either perpendicular or parallel to the vitreal surface and processed by double-label immunofluorescence techniques using antibodies directed to VIP, GABA, TH, and SRIF. The immunoreactive staining patterns obtained with these antibodies were the same as those described in previous studies. GABA-IR neurons were localized to the proximal inner nuclear layer (INL) and ganglion cell layer (GCL) and processes were distributed throughout the inner plexiform layer (IPL). TH- and SRIF-IR neurons were sparsely distributed to the proximal INL and GCL, respectively. TH-IR processes ramified in laminae 1, 3, and 5, and SRIF-IR processes in laminae 1 and 5 of the IPL. Colocalization experiments showed that all VIP-IR neurons contain GABA immunoreactivity. In contrast, colocalization of VIP and TH or SRIF immunoreactivities was never observed. These results demonstrate that VIP-IR wide-field amacrines of the rabbit retina make up a neurochemically and morphologically distinct subpopulation of the GABA-IR amacrine cell population. Furthermore, VIP-IR amacrine cells constitute a distinct group with respect to the TH- and SRIF-IR amacrine cells.
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PMID:Colocalization of vasoactive intestinal polypeptide and GABA immunoreactivities in a population of wide-field amacrine cells in the rabbit retina. 134 29

Thirty-eight gestating sows were either immunized against somatostatin (SRIF) and/or injected with growth hormone-releasing factor (GRF). Treatment effects on carcass composition and resistance of newborn piglets to a 60-hour fast were investigated. Protein content of carcasses at birth was increased in piglets of sows receiving GRF or immunized against SRIF, however, when sows received both treatments there was a reduction in carcass protein content (p = 0.01). Other carcass components were unaltered by treatments, and none of the treatments affected metabolic or endocrine profiles of piglets at birth. Concentrations of GH, IGF-I (p less than 0.01), glucagon and cortisol (p less than 0.05) increased linearly with duration of fast, whereas glucose values decreased. Resistance to fasting was unaltered in piglets from any treatment thereby suggesting that exogenous GRF and/or SRIF immunization of sows during gestation are unlikely to improve survival of newborn piglets.
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PMID:Carcass composition and resistance to fasting in neonatal piglets born of sows immunized against somatostatin and/or receiving growth hormone-releasing factor injections during gestation. 134 59

Several somatostatin analogs with recently synthesized acetylated N terminus were assayed in vivo for their effects on sodium pentobarbital-stimulated growth hormone (GH) levels in fed male rats and gastrin-releasing peptide (14-27)-stimulated gastrin levels in fasted male rats. The binding characteristics of these analogs to somatostatin receptors were also examined in various human tumors and normal tissues. The analog RC-101-I, injected at a dose of 0.1 micrograms/100 g body wt, significantly suppressed GH release (P less than 0.01) for at least 2 hr. Analog RC-160-II caused the longest inhibition of GH release, greater than that induced by nonacetylated parent analog RC-160, with GH levels showing significant suppression (P less than 0.01) for more than 3 hr. Analogs RC-160-II and RC-101-I and RC-160, injected at a dose of 1.0 micrograms/100 g body wt, significantly (P less than 0.01) suppressed gastrin-releasing peptide (14-27)-stimulated serum gastrin. Analog RC-101-I was active in this test at a dose of 0.1 micrograms/100 g body wt. RC-160-II showed significant binding to somatostatin-14 receptors in all investigated tissues (human colon, human colon cancer, breast cancer, human pancreas and pancreatic cancer, human prostate and prostate cancer, and rat cerebral cortex), but there were marked variations in binding affinities among various normal and cancerous tissues. The highest affinity was found in membranes of colon cancer (Ka = 18.4 nM-1) and breast cancer (Ka = 12.46 nM-1). The binding affinity of RC-160-II to somatostatin receptors in membranes of the breast cancer was similar to that of RC-160. RC-101-I showed higher binding affinity to somatostatin-14 receptors than RC-160 in human breast, pancreatic, and prostate cancer. With the exception of breast cancer tissue, the binding affinity of RC-101-I was significantly lower than that of RC-160-II in membranes of all investigated tissues. It can be concluded that acetylated somatostatin analogs RC-101-I and RC-160-II possess prolonged and enhanced biological activities in suppressing serum GH and gastrin in rats. Significant variations in binding affinities for these analogs in different tissues and various tumors suggest that differences may exist between somatostatin receptors in normal versus malignant tissues. This raises the possibility that some of these analogs could be used more selectively in the treatment of various neoplasms.
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PMID:Biological activity and receptor binding characteristics to various human tumors of acetylated somatostatin analogs. 134 89


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