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)

Calcitonin gene-related peptide (CGRP)-I has been reported to inhibit gastric acid secretion through stimulation of gastric somatostatin-14 (S-14) release. To establish whether some of the effects of CGRP-I on intestinal function might also be mediated through somatostatin, fetal rat intestinal cultures were treated with test agents for 2 h, and the secretion of somatostatin-like immunoreactive (SLI) peptides was determined by RIA. The intestinal cultures have been previously found to synthesize and secrete both major forms of intestinal somatostatin (S-28 and S-14). Rat (r) CGRP-I treatment of the intestinal cultures stimulated SLI secretion to 163 +/- 33% of the control level at 3.3 x 10(-7) M (P < 0.01) and 227 +/- 30% of the control level at 10(-6) M (P < 0.001). In contrast, the structurally related peptide, human CGRP-II, had no effect on total SLI release at any concentration up to 10(-6) M. Gel permeation chromatography revealed that rCGRP-I increased the secretion of S-14 by 22 +/- 6-fold (P < 0.01) compared to the control value, whereas that of S-28 increased nonsignificantly by only 2 +/- 1-fold. Thus, the ratio of S-28 to S-14 secreted into the medium decreased from 1.7 +/- 0.2 in control medium to 0.2 +/- 0.3 after rCGRP-I treatment (P < 0.01). As the ratio of S-28 to S-14 stored by the cells was not altered by rCGRP-I treatment, these findings suggest that intestinal S-28 and S-14 may be secreted by two distinct intestinal D-cells with different sensitivities to rCGRP-I or by a single D-cell type containing distinct pools of S-14 and S-28 that have different sensitivities to rCGRP-I. The results of these in vitro studies further indicate that in vivo, CGRP-I may modulate aspects of intestinal function through its stimulation of the secretion of S-14.
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PMID:Calcitonin gene-related peptide-I preferentially stimulates secretion of somatostatin from intestinal cultures. 790 70

Somatostatin (SRIF) is a widely distributed regulatory peptide. Recently, it was shown that human seminal plasma contains high concentrations of SRIF. In order to find the cellular source of seminal SRIF we have examined the presence of SRIF in porcine urogenital tissues. The concentration of SRIF in male accessory reproductive tissues of 3-month-old pigs (N = 4) ranged from 1 to 17 nmol/kg. In the boar, only the prostate gland contained significant amounts of SRIF (median 7 nmol/kg, range 3-18 nmol/kg, N = 4). Testis and semen contained no SRIF. Gel chromatography of extracts of the male accessory sex glands and epididymis showed both SRIF-28 and SRIF-14, whereas urinary bladder contained mainly SRIF-14. In conclusion, the results show a considerable species, tissue and developmental variation in the expression of SRIF in the genitourinary tract.
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PMID:Somatostatin in the boar reproductive system. 791 91

The somatostatin (SS) gene is transcriptionally regulated via the cyclic AMP (cAMP) response element (CRE), located in the proximal promoter (-41 to -48 bp). We have previously reported that glucocorticoids induce dose-dependent cell-specific alterations in the steady-state SS mRNA level. Here we have investigated direct transcriptional control of the SS gene by glucocorticoids. We have examined transcriptional interaction between glucocorticoids and the cAMP signalling pathway and mapped the 5' upstream regulatory region of the SS gene involved in glucocorticoid transactivation. Transcriptional regulation was determined by analysis of chloramphenicol acetyltransferase (CAT) activity in PC12 rat pheochromocytoma cells and A126-1B2 (protein kinase A-deficient mutant PC12) cells, by acute transfection of 5' flanking SS DNA (- 750, -250 and -71 bp) ligated to the reporter (CAT) gene. Dexamethasone (DEX) induced a dose-dependent 2.2-fold stimulation of SS gene transcription in PC12 cells, but not in A126-1B2 cells. Other steroid and thyroid hormones tested, and retinoic acid, were ineffective, while cAMP and forskolin stimulated gene transcription 4-5-fold in PC12 cells but not in A126-1B2 cells. DEX exerted an additive effect on cAMP-induced gene transcription. Deletion of the promoter from -750 to -71 bp (but not from -750 to -250 bp) abolished all stimulatory effects of DEX without affecting cAMP responsiveness. Mutation of the CRE abrogated both DEX- and cAMP-dependent gene enhancement. Gel electrophoretic mobility shift assays confirmed that the -250 to -71 bp region of the SS promoter (but not the -71 to +55 bp domain) binds specifically to a glucocorticoid response element-sensitive nuclear protein(s) from PC12 cells, suggesting a putative glucocorticoid receptor interaction with SS promoter DNA. We conclude that glucocorticoids regulate SS gene transcription positively. Glucocorticoid-induced transactivation shows dependence on protein kinase. A activity, and may be mediated via protein-protein interaction between the glucocorticoid receptor and the CRE binding protein. DNA sequences upstream from the CRE between -250 and -71 bp in the SS promoter appear to be the target of glucocorticoid action.
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PMID:Glucocorticoids activate somatostatin gene transcription through co-operative interaction with the cyclic AMP signalling pathway. 791 2

Previously it has been shown that vasopressin (VP) and oxytocin are converted by aminopeptidase activity in brain membranes into fragments with potent CNS activities. This report concerns the properties of this enzyme activity, addressed as VP-converting aminopeptidase (VP-AP) activity, in membranes of the rat brain. The VP-AP activity had a pH optimum at pH 7.0 and had a Km of 17 microM for its action on VP. Amastatin was the most potent aminopeptidase inhibitor. Enzyme activity was inhibited by relatively low concentrations of metal chelators. Treatment of brain membranes by EDTA resulted in loss of enzyme activity that was completely reversed by 10 microM Zn2+, indicating that VP-AP activity is a metallopeptidase. Several VP analogues and fragments, in particular VP(1-8), inhibited the action of enzyme activity on VP. Among peptides unrelated to VP, angiotension I, somatostatin, and porcine ACTH(1-39) markedly inhibited enzyme activity. Solubilization of VP-AP activity from brain membranes and gel filtration on Sephadex G200 showed two peaks of activity, one eluting with an apparent mass of about 140 kDa, the other in the void volume. Gel filtration fractions were able to convert [3H][Phe3]VP in a step-wise fashion. The VP-AP-like activity was found in many tissues outside the brain. Highest activity was present in lung, kidney, parts of the gastrointestinal tract, ovary, and uterus. The results indicate that VP-AP activity is a widely distributed enzyme with probably multiple functions, one of which involves the metabolism of vasopressin in the brain.
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PMID:Properties of aminopeptidase activity involved in the conversion of vasopressin by rat brain membranes. 799 91

Peptides such as somatostatin (SS14), epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and insulin-like growth factors (IGF-I and IGF-II) are present in breast milk from various species, and their significance in the developing gastrointestinal tract has been suggested. Our recent studies have indicated that rat milk soluble fraction (RMSF) protects SS14 in the gastrointestinal lumen by inhibiting in vitro the luminal peptidolysis. In the present studies, we have shown that RMSF inhibited in vitro degradation by midjejunal luminal flushings of suckling rats of 125I-labeled somatostatin 14[Tyr11], EGF, TGF alpha, IGF-I and IGF-II, as well as trypsin activity in vitro against benzoyl-L-arginyl-p-nitroanilide. The inhibitory factors present in the RMSF were further fractionated by gel filtration on Sephadex G100, ion-exchange chromatography on DEAE-Sephadex, and fast protein liquid chromatography (FPLC). Gel filtration of Sephadex G100 separated RMSF into three peaks of proteins: G1, G2, and G3; peptidase inhibitor activities were present exclusively in G1. Ion-exchange chromatography on DEAE-Sephadex column resolved peptidase inhibitory activity (G1) into three different peaks, D1, D2, and D3, eluted at sodium chloride concentrations of 0.05 M, 0.1 M, and 0.2 M, respectively. Further purification of D2 by FPLC resulted in a fraction rich in peptidase inhibitory activity, which was essentially free of trypsin inhibitory activity. Results indicate the presence of at least three peptidase inhibitors in rat milk, which may play a role in the protection of milk-borne peptides in the gastrointestinal lumen.
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PMID:Presence of multiple forms of peptidase inhibitors in rat milk. 814 98

Androgen and androgen receptor (AR) play an important role in sexual differentiation and prostate proliferation. To investigate AR gene transcriptional regulation, a 2.3-kilobase AR gene promoter region was isolated, sequenced, and characterized. Chloramphenicol acetyltransferase (CAT) assay and sequence homology search of AR gene promoter among human, rat, and mouse revealed some potential cis-acting elements, including a GC box, a suppressor region, and a purine-rich element. Deletion analysis and gel retardation assay using a 50-base pair (bp) double-strand purine-rich element showed that this purine-rich element can bind to specific proteins in nuclear extract of LNCaP and HeLa cells and may be essential for AR gene transcription. Furthermore, to investigate the effect of cAMP on AR gene transcription, we treated LNCaP and HeLa cells with 10 mM (Bu)2cAMP after transfection with CAT gene reporter plasmids linked to the AR gene promoter. This treatment induced several folds of CAT activity in LNCaP cells only, and the induction was further confirmed at AR mRNA level by Northern blot analysis and reverse transcription-polymerase chain reaction assay. Deletion analysis of the AR gene promoter showed that a region between 530 bp and 380 bp upstream of AR gene transcription initiation site, which includes one potential cAMP response element (CRE), is responsible for cAMP induction. Gel retardation analysis using this CRE (AR/CRE1) showed that AR/CRE1 can bind to specific proteins in nuclear extract of LNCaP cells, which appears to form a different binding complex compared to somatostatin/CRE.
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PMID:Identification of 3',5'-cyclic adenosine monophosphate response element and other cis-acting elements in the human androgen receptor gene promoter. 815 32

Much knowledge was accumulated in the regulation of plasma renin activity and renin secretion during recent years. However, the mechanisms of renin gene transcription, especially for the human gene, have been poorly studied because of the lack of cell lines expressing renin. Cells derived from chorion tissue were used to study renin gene transcription because these cells express renin and regulate renin secretion in a similar way to JG cells. The present study was performed to determine the cis-regulatory elements and the trans-acting factors involved in human renin gene expression using chorionic cells. Transient DNA transfections were performed with various constructs containing the 5'-flanking region of the human renin gene. 5'-Deletion analysis of the human renin promoter (from -2616 to -67 bp) revealed the presence of two proximal negative cis-regulatory elements between -374 and -273 bp and between -273 and -137 bp. These elements were not present in a non-renin-producing cell line, JEG-3 cells. DNase I footprinting revealed that two sequences located within these regions bind trans-factors present in chorionic cellular nuclear extract: AGE3-like sequence (-293/-273) and apolipoprotein A1 regulatory protein-1-like sequence (-259/-245). The first 110 bp of the renin promoter were sufficient to direct specific expression in chorionic cells and contained two footprints sharing homology with ets (-29/-6) and pituitary-specific factor (Pit-1) (-70/-62) sequences. Furthermore, one footprint (-234/-214) contained the sequence TAGCGTCA, which shares strong homology to the cAMP-responsive element (CRE) binding site. Gel shift analysis showed specific DNA/protein complexes within this region, which were displaced by the somatostatin consensus CRE. Finally, luciferase analysis of 5'-deletion mutant revealed that -273 to +16 bp of the renin promoter was sufficient to confer complete forskolin stimulation, whereas deletion to -130 (deletion of the CRE) decreased cAMP responsiveness by 50% and those to -67 bp (deletion of the CRE and Pit-1-like sequences) suppressed it. Thus, these latter two sequences probably act together to confer complete cAMP responsiveness.
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PMID:cis-regulatory elements and trans-acting factors directing basal and cAMP-stimulated human renin gene expression in chorionic cells. 815 25

1. Among the consequences of H. pylori infection is an increase in gastric acid secretion due to the impairement in feedback inhibition by somatostatin. Here, we show that lipopolysaccharide from H. pylori inhibits the binding of somatostatin to gastric mucosal receptor, and that antiulcer agents, ebrotidine and sulglycotide, are capable of countering this effect. 2. The somatostatin receptor was prepared from the solubilized gastric mucosal epithelial cell membranes by affinity chromatography on Affi-Gel-bound [D-Tryp8] SRIF-14 and used in the binding assays for 125I-labeled somatostatin in the presence of H. pylori lipopolysaccharide and antiulcer agents. 3. The assays revealed a dose-dependent inhibition in the receptor-somatostatin binding by the lipopolysaccharide which reached a maximum of 94.1%. The effect of H. pylori lipopolysaccharide was countered by ebrotidine and sulglycotide, which at their optimal doses produced 94.9% and 84% restoration in somatostatin-receptor binding, respectively. 4. The results demonstrate that the antiulcer agents, ebrotidine and sulglycotide, possess the ability to counteract the H. pylori interference with somatostatin regulatory effect on gastric acid secretion.
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PMID:Reversal of gastric somatostatin receptor inhibition by Helicobacter pylori lipopolysaccharide with ebrotidine and sulglycotide. 918 6

Glucagon-like peptide-1(7-36NH2) is a potent stimulator of insulin secretion, as well as of somatostatin-14 (SS-14) release from the pancreatic and gastric D-cells. To investigate the possible effects of this peptide on release of intestinal somatostatin (SS-28 and SS-14, rat intestinal cultures were treated with 10(-12)-10(-6) M GLP-1(7-36NH2), as well as with the structurally related peptides, GLP-1(1-36NH2) and GLP-2. Both forms of GLP-1 stimulated does-dependent increases in intestinal somatostatin; secretion reached 643 +/- 126% of controls (p < 0.001) after treatment with 10(-6) M GLP-1(7-36NH2), and 398 +/-76% of controls (p < 0.001) after 10(-6) M GLP-1(1-36NH2). Thus, GLP-1(7-36NH2) was more effective than GLP-1(1-36NH2) in stimulating secretion of intestinal somatostatin-like immunoreactivity (SLI) (p < 0.05). GLP-2 did not affect intestinal somatostatin release. Gel permeation analysis demonstrated that 10(-6) M GLP-1(7-36NH2) stimulated SS-28 by 2.9 +/- 0.4-fold and SS-14 by 9.1 +/- 3.7-fold, whereas GLP-1(1-36NH2) exerted equivalent effects (2.8 +/- 0.9-fold) on both forms of somatostatin. These findings define a novel biological role for GLP-1(7-36NH2) in the regulation of intestinal somatostatin secretion, and demonstrate that GLP-1(1-36NH2) exerts unique biological activities in this system.
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PMID:Truncated and full-length glucagon-like peptide-1 (GLP-1) differentially stimulate intestinal somatostatin release. 922 22

In this study, we investigated the inhibitory effect of Helicobacter pylori lipopolysaccharide on the binding of somatostatin to gastric epithelial cell membrane receptor, and assessed the effect of antiulcer agent, sucralfate, on this process. The assays conducted with the somatostatin receptor, purified from the solubilized epithelial cell membranes by affinity chromatography on Affi-Gel-[D-Tryp8]SRIF-14, revealed a dose-dependent inhibition in receptor-somatostatin binding by the lipopolysaccharide which reached a maximum of 94.1%. This effect of H. pylori lipopolysaccharide was countered by sucralfate that produced a 92.5% restoration in receptor-somatostatin binding at 70 micrograms/ml of the drug. The findings demonstrate that sucralfate is capable of reversing the interference by H. pylori lipopolysaccharide with somatostatin-receptor binding on gastric mucosal G-cells.
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PMID:Helicobacter pylori lipopolysaccharide inhibition of gastric somatostatin receptor: effect of sucralfate. 924 12


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