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)

Seven synthetic analogues of somatostatin helped clarify structural requirements for suppression of growth hormone secretion in rats. Size of the ring is not critical; deletions of serine-13, lysine-4 or asparagine-5 result in peptides which retain an appreciable fraction of the activity. The analogue des-Ala1, Gly2, Asn5-somatostatin lowers plasma growth hormone and insulin levels without affecting plasma glucagon levels significantly.
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PMID:Structure activity studies on somatostatin. 105 80

Antral gastrin secretion and gene expression is inhibited by the paracrine release of somatostatin from antral D cells. Transforming growth factor-alpha and epidermal growth factor (EGF) stimulate gastrin reporter gene constructs when transfected into pituitary GH4 cells. Somatostatin inhibits EGF stimulation of gastrin gene expression, which is in part mediated at the level of transcriptional regulation as somatostatin inhibits EGF stimulation of gastrin reporter gene constructs. Somatostatin inhibition was abolished by pertussis toxin, indicating somatostatin inhibits transcription through the inhibitory G protein Gi. Somatostatin inhibition was unaffected by vanadate and okadaic acid, implying this inhibitory pathway is mediated neither through phosphotyrosine phosphatases nor serine/threonine phosphatases, respectively. Gastrin reporter genes containing 82 base pairs of the 5'-flanking DNA were sufficient to confer both EGF responsiveness and inhibition by somatostatin in GH4 cells. However, transcription of a gastrin reporter gene construct containing only the EGF response element (GGGGCGGGGTGGGGGG), located at -68 to -53, was stimulated by EGF but was not inhibited by somatostatin. Thus, somatostatin inhibits EGF-stimulated gastrin gene transcription by a mechanism other than by interfering with cell signals elicited by the EGF receptor. Since the 82 GASCAT is inhibited by somatostatin, this result also implies that sequences adjacent to the EGF response element contain a cis-regulatory element mediating transcriptional inhibition by somatostatin. This cis-element was located using gastrin reporter genes comprising sequential segments of the human gastrin promoter sequence from the transcriptional start site to -82 in the 5'-flanking DNA. Gastrin oligonucleotide constructs lacking the D oligonucleotide (gatcCATATGGCAGGGTA), located at -82 to -69 in the 5'-flanking DNA, were not inhibited by somatostatin, indicating that a somatostatin inhibitory cis-element is located between -82 and -69 in the 5'-flanking DNA of the human gastrin promoter.
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PMID:Identification of a cis-regulatory element mediating somatostatin inhibition of epidermal growth factor-stimulated gastrin gene transcription. 135 47

An implanted stimulating device chronically stimulated the left cervical vagus nerve in epileptic patients. Cerebrospinal fluid concentrations of free and total gamma-aminobutyric acid, homovanillic acid, 5-hydroxyindoleacetic acid, aspartate, glutamate, asparagine, serine, glutamine, glycine, phosphoethanolamine, taurine, alanine, tyrosine, ethanolamine, valine, phenylalanine, isoleucine, vasoactive intestinal peptide, beta-endorphin, and somatostatin were measured before and after 2 months of chronic stimulation in six patients. Significant increases were seen in homovanillic acid and 5-hydroxyindoleacetic acid in three patients, and significant decreases in aspartate were seen in five patients. These changes were associated with a decrease in seizure frequency.
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PMID:Neurochemical effects of vagus nerve stimulation in humans. 150 37

An endopeptidase was isolated from Xenopus laevis skin secretions. This enzyme, which has an apparent molecular mass of 100 kDa, performs a selective cleavage at the Xaa-Phe, Xaa-Leu, or Xaa-Ile bond (Xaa = Ser, Phe, Tyr, His, or Gly) of a number of peptide hormones, including atrial natriuretic factor, substance P, angiotensin II, bradykinin, somatostatin, neuromedins B and C, and litorin. The peptidase exhibited optimal activity at pH 7.5 and a Km in the micromolar range. No cleavage was produced in vasopressin, ocytocin, minigastrin I, and [Leu5]enkephalin, which include in their sequence an Xaa-Phe, Xaa-Leu, or Xaa-Ile motif. The endopeptidase activity was inhibited by divalent cation chelators and by phosphoramidon only at high concentrations (IC50 = 50 microM), whereas it was insensitive to classical inhibitors of chymotrypsin, angiotensin convertase, and serine and cysteine peptidases, as well as carboxypeptidases. It is hypothesized that this enzyme, which is distinct from neutral endopeptidase (EC 3.4.24.11), constitutes the prototype of a family of related metalloendopeptidases that inactivate peptide substrates by cleavage at the Xaa-Phe, Xaa-Leu, or Xaa-Ile bond.
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PMID:A peptide-hormone-inactivating endopeptidase in Xenopus laevis skin secretion. 172 23

The effects of glucagon deficiency and excess on plasma leucine, lysine, and alanine were examined in six healthy young adult men, with primed continuous infusions of L-[1-13C]- or L-[5,5,5-2H3]leucine, L-[alpha-15N]-lysine, and L-[3-13C]alanine for 150 min before and during 210 min of either a glucagon-deficient euglycemic state (experiment 1), a basal glucagon state (experiment 2), or a glucagon-excess state (experiment 3). Steady-state plasma hormone levels were achieved by infusion of somatostatin (250 micrograms/h) and insulin (0.07 mU.kg-1.min-1), without (experiment 1) or with an infusion of glucagon at 0.7 ng.kg-1.min-1 (experiment 2) or 2.5 ng.kg-1.min-1 (experiment 3). Plasma branched-chain amino acid (AA) concentrations did not change with altered glucagon status, whereas significant differences were observed for plasma lysine, alanine, glycine, serine, threonine, proline, tyrosine, citrulline, and ornithine levels (0.05 greater than P greater than 0.001). Plasma leucine, lysine, and alanine fluxes and the rate of de novo alanine synthesis showed no significant changes with either glucagon deficiency or excess. These findings lead to the conclusion that glucagon-induced alterations in plasma AA profiles are not due to changes in the rate of appearance of AA from peripheral tissues but rather a consequence of changes in the fate of AA within the splanchnic region.
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PMID:Plasma amino acid kinetics during acute states of glucagon deficiency and excess in healthy adults. 196 9

The chelonians occupy an important position in phylogeny representing a very early branching from the ancestral reptile stock. Hormonal polypeptides in an extract of the pancreas of the red-eared turtle were purified to homogeneity by reversed phase HPLC and their primary structures were determined. Turtle insulin is identical to chicken insulin. Turtle glucagon differs from chicken glucagon by the substitution of a serine by a threonine residue at position 16 and from mammalian glucagon by an additional substitution of an asparagine by a serine residue at position 28. Turtle pancreatic somatostatin is identical to mammalian somatostatin-14. The crocodilians are phylogenetically much closer to the birds than are the chelonians. Alligator insulin, however, contains three amino acid substitutions relative to chicken insulin. Thus, caution is required when inferring phylogenetic relationships based upon a comparison of amino acid sequences of homologous peptides.
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PMID:Isolation and structural characterization of insulin, glucagon and somatostatin from the turtle, Pseudemys scripta. 197 47

From rat brain, a membrane bound substance P-degrading endopeptidase (SPE) was purified 1580 fold to near homogeneity. After extraction with 10 mM CHAPS, the enzyme preparation was subjected to ion exchange chromatography on DEAE-cellulose, adsorption chromatography on hydroxyapatite, gelfiltration through Ultrogel AcA 44 and FPLC on Mono Q. This enzyme of 70,000 molecular weight is optimally active at pH 7.5. Metal chelators (EDTA and EGTA) and sulfhydryl modifying reagents (N-ethylmaleimide and p-chloromercuriphenylsulfonic acid) are strongly inhibitory while the serine-protease inhibitor diisopropyl-fluorophosphate does not effect the enzyme activity. The enzyme is strongly inhibited by bacitracin but not by phosphoramidon and captopril. Degradation of substance P is strongly inhibited by neurotensin, somatostatin, ACTH 1-39, and less effectively by LHRH but not by Leucine-enkephalin. Substance P is preferentially hydrolyzed at the Gln6-Phe7 peptide bond but fragmentation at the Pro4-Gln5, Gln5-Gln6,Phe7-Phe8 and Gly9-Leu10 bonds was also observed.
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PMID:A membrane bound substance P degrading endopeptidase from rat brain. 244 28

A 43-kDa DNA binding protein which recognizes the TGACGTCA element of the rat somatostatin promoter has been purified from rat brain. Purification of the protein involved initial separation of three sequence-specific binding activities, b1-b3, from each other using DEAE-Sepharose chromatography. The protein corresponding to the b2 complex was further purified to apparent homogeneity by two cycles of sequence-specific DNA affinity chromatography, yielding a single species with an apparent mass of 43,000 daltons on a silver-stained polyacrylamide gel. Sequence-specific DNA binding of this purified protein was demonstrated by Southwestern blotting, renaturation, and DNase I footprinting studies. The 43-kDa protein was phosphorylated on serine residue(s) by the catalytic subunit of cAMP-dependent protein kinase, as shown by phosphoamino acid analysis. Furthermore, the purified protein specifically stimulated transcription from the rat somatostatin promoter in an in vitro transcription system. These results indicate that this 43-kDa protein is a transcription factor required for somatostatin gene expression.
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PMID:Purification and characterization of a 43-kDa transcription factor required for rat somatostatin gene expression. 256 50

Regulatory effects of insulin, somatostatin and cholecystokinin on amino acid transport in the isolated perfused rat pancreas have been studied using a rapid dual isotope dilution technique. Uni-directional L-serine transport (15 s) was quantified relative to an extracellular tracer D-mannitol over a wide range of substrate concentrations. In pancreata perfused with 2.5 mmol/l D-glucose, a weighted nonlinear regression analysis of overall transport indicated an apparent Km = 14.4 +/- 1.6 mmol/l and Vmax = 25.9 +/- 1.4 mumol.min-1.g-1 (n = 6). Although L-serine transport was stimulated during perfusion with 100 microU/ml bovine insulin, endogenous insulin (7-25 ng.min-1.g-1) released during continuous perfusion with either 8.8 mmol/l or 16.8 mmol/l D-glucose had no such effect. Exogenous somatostatin-14 (250 pg/ml) or cholecystokinin octapeptide (CCK-8, 3 x 10(-11) mol/l) appeared to increase only the Km for transport. Only CCK-8 evoked a notable protein output (2.9 +/- 0.3 mg.30 min-1.g-1) and juice flow (68 +/- 10 microliters.30 min-1.g-1, n = 3) from the exocrine pancreas. When pancreata were perfused with bovine insulin (100 microU/ml) and somatostatin-14 (250 pg/ml), the stimulatory action of exogenous insulin on L-serine transport was abolished. If endogenous insulin and somatostatin, released concurrently in response to 16.8 mmol/l D-glucose, were conveyed to the exocrine epithelium via an islet-acinar portal axis, it is conceivable that somatostatin modulates the stimulatory action of insulin on basolateral amino acid transport in the exocrine pancreas.
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PMID:Paradoxical effects of endogenous and exogenous insulin on amino acid transport activity in the isolated rat pancreas: somatostatin-14 inhibits insulin action. 256 59

The serine proteinase glandular kallikrein has been demonstrated in the gastrointestinal tract, although there is some doubt as to whether it is synthesized there or derives from exocrine-gland secretions. Using a rat pancreatic kallikrein cRNA probe we have demonstrated kallikrein-like gene expression in the corpus, duodenum, jejunum, ileum, caecum and colon, and compared the pattern of expression with that of the gastrointestinal peptides somatostatin, gastrin and glucagon. In addition, using a panel of oligonucleotide probes specific for various members of the rat kallikrein-gene family, we have shown that the kallikrein-like gene expressed appears to be expressed as true kallikrein.
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PMID:Kallikrein-gene expression in the rat gastrointestinal tract. 260 9


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