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 effect of a purified somatostatin monoclonal antibody, SOMA 10, and its Fab fragments on gastrin release have been examined in the isolated perfused rat stomach. SOMA 10 was purified from ascites fluid by ammonium sulfate precipitation followed by hydroxylapatite (HAP) chromatography. This gave a preparation of greater than 90% purity, as assessed by fast affinity and size exclusion high-performance liquid chromatography (HPLC). HAP-purified SOMA 10 had a binding capacity of 760 mmol somatostatin/mol antibody, a dissociation constant of 2.2 nM, and recognized amino acid residues 5-12 of the somatostatin molecule. Fab fragments of SOMA 10 were prepared and purified by protein A affinity chromatography, and the purity assessed by HPLC and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Single passage perfusion of SOMA 10 (100 micrograms/ml) into the gastric vasculature caused a paradoxical decrease in basal gastrin release. However, recirculation of the antibody (20 micrograms/ml) caused an increase in cumulated gastrin release. Perfusion of Fab fragments of SOMA 10 (66 micrograms/ml) also increased gastrin secretion. These results support the suggestion that somatostatin exerts a tonic restraint on gastrin release and that penetration of the antibody to the site of somatostatin release is necessary for it to have an effect.
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PMID:Effect of a purified somatostatin monoclonal antibody and its Fab fragments on gastrin release. 170 49

The effect of the long-acting somatostatin analogue, octreotide acetate (Sandostatin) on enzyme elevation after endoscopic pancreatography was studied in a prospective, randomized, double-blind trial. Sixty-three consecutive patients undergoing ERCP were randomly allocated to two group. In the control group, 34 patients received isotonic sodium-chloride, and in the treated group 29 patients received 0.1 mg of octreotide acetate subcutaneously before the pancreatography. After the endoscopy, amylase levels increased to pathological range in 15 of the controls and in 3 of the treated patients, whereas lipase levels showed a pathological rise in 17 of the controls and in 5 of the treated patients. A significant difference (p less than 0.01) was observed in the amylase and lipase changes between the two groups at 90 and 180 min after pancreatography. The enzyme levels showed at 90 min, mean +/- SD amylase: controls 540 +/- 185 units/liter, treated patients 261 +/- 108 units/liter; lipase: controls 304 +/- 98 units/liter, treated patients 198 +/- 88 units/liter. These findings suggest that the use of long-acting somatostatin analogue ameliorates the enzyme increases in the serum after endoscopic pancreatography.
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PMID:The effect of long-acting somatostatin analogue on enzyme changes after endoscopic pancreatography. 170 82

Isolated sheep thyroid follicles release specific insulin-like growth factor-binding proteins (IGFBPs). Since IGFBPs can modulate IGF bioactivity, at least in vitro, their presence in thyroid tissue may influence synergistic interactions between TSH and endogenous IGF-I or -II which are known to control both thyroid growth and function. We have examined the hormonal control of IGFBP release in relation to iodine organification. Sheep thyroid follicles were isolated by incubation with collagenase and differential centrifugation, grown in Coon's modified Ham's F12M medium with the addition of transferrin, glycylhistidyl-lysine, somatostatin (3H), TSH, cortisol and insulin (6H), and maintained in OH (hormone-free) or 3H medium with or without further supplements for 48 h. Conditioned culture medium was separated by 8% sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis, transferred to nitrocellulose and incubated with 125I-labelled IGF-II followed by autoradiography (ligand blot). Additionally, the radioactive bands were cut from the filters and quantified by gamma-spectrometry. Iodine organification was assessed by incubation of follicles with 10(6) c.p.m. Na125I for 3 h before washing, solubilization in 0.1 mol NaOH/l and the precipitation of organified radioisotope with 10% (v/v) trichloroacetic acid. Cells conditioned in OH or 3H medium released specific IGFBPs of 46, 34, 28 and 19 kDa on ligand blot analysis. The proteins of 34 and 19 kDa were immunopositive on Western blot analysis using anti-bovine IGFBP-2 antiserum. The 46-kDa IGFBP was retained by Concanavalin A-Sepharose chromatography and demonstrated to be glycoprotein. This is probably ovine IGFBP-3. The addition of TSH, or TSH plus cortisol to OH or 3H medium significantly decreased the 125I-labelled IGF-II associated with the 34- and 28-kDa IGFBP species. All IGFBP species were substantially reduced in 6H medium, which was predominantly due to the effects of TSH and cortisol. When total 125I-labelled IGF-II associated with IGFBPs was considered, a significant (P less than 0.01) inverse correlation existed between IGFBP activity and iodine organification in the same cultures; the latter being greatest in OH or 3H medium supplemented with TSH and cortisol. None of these hormone additions altered the endogenous release of IGF-II by the cells. These results suggest that endogenous IGFs, under hormonal control, may modulate the action of endogenous IGF in the regulation of thyroid function.
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PMID:Hormonal regulation of insulin-like growth factor (IGF)-binding proteins secreted by isolated sheep thyroid epithelial cells: relationship with iodine organification. 171 78

Mast cells of the human skin not only release mediators following immunological activation, but may also be stimulated to release histamine by the neuropeptides substance P, vasoactive intestinal polypeptide and somatostatin or by other basic secretagogues such as morphine, poly-L-lysine and compound 48/80. Release of histamine under these conditions is rapid and accompanied by minimal generation of the eicosanoids, prostaglandin (PG)D2 and leukotriene (LT)C4. Transient elevations of intracellular calcium are associated with mediator secretion induced by both stimuli, that induced by anti-IgE being derived from extracellular sources through channels in the plasma membrane while that stimulated by neuropeptides is mobilized intracellularly. Similarly, elevations of intracellular cyclic adenosine monophosphate (AMP) induced by anti-IgE occur only in the presence of extracellular calcium whereas with substance P elevations are apparent even in the absence of extracellular calcium. With the latter stimulus, histamine release is complete before the peak cyclic AMP is achieved. Histamine release stimulated by both secretagogues is unaffected by sodium cromoglycate or nedocromil sodium but is reduced by both salbutamol and isobutylmethylxanthine. Despite these biochemical and temporal differences, degranulation induced by both secretagogues proceeds by compound exocytosis which is indistinguishable under the electron microscope.
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PMID:Mediator secretion from human skin mast cells provoked by immunological and non-immunological stimulation. 172 14

A serum-free culture medium (defined medium = DM) was elaborated by adding to Eagle's minimum essential medium (MEM), non-essential amino acids, transferrin, putrescine, tripeptide glycyl-histidyl-lysine, somatostatin, sodium selenite, ethanolamine, phosphoethanolamine, sodium pyruvate, and metal trace elements. This medium was tested for its ability to support sustained surfactant biosynthesis in fetal alveolar epithelial type II cells. For up to 8 days, ultrastructure was maintained with persistence of lamellar inclusion bodies. Thymidine incorporation into DNA was enhanced about 50% in DM as compared with MEM, whereas it was enhanced 300% in 10% fetal bovine serum. With DM, the incorporation of tritiated choline into phosphatidylcholine (PC) of isolated surfactant material was about twice that with MEM. Deletion experiments evidenced the prominent role of pyruvate, transferrin, and selenium in the stimulation of surfactant PC biosynthesis. The addition of biotin to DM enhanced surfactant PC biosynthesis slightly and nonsurfactant PC biosynthesis markedly. The presence of nucleosides seemed unfavorable to the synthesis of surfactant PC. Type II cells responded to the addition of epidermal growth factor and insulinlike growth factor-I both by increased thymidine incorporation into DNA and choline incorporation into PC. It is concluded that DM represents a useful tool for cultivating type II cells without loss of their specialized properties and for studying the regulation of cell proliferation and surfactant biosynthesis in a controlled environment.
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PMID:Culture of fetal alveolar epithelial type II cells in serum-free medium. 174 24

The effects of glucagon on water and electrolyte transport in the kidney were investigated on hormone-deprived rats, i.e. thyroparathyroidectomized diabetes insipidus Brattleboro rats infused with somatostatin. Glucagon consistently inhibited the reabsorption of water and Na+, Cl-, K+ and Ca2+ along the proximal tubule accessible to micropuncture, leaving the reabsorption of inorganic phosphate (Pi) untouched. In the loop, besides its previously described stimulatory effects on Na+, Cl-, K+, Ca2+ and Mg2+ reabsorption, glucagon strongly inhibited Pi reabsorption, very probably in the proximal straight tubule. These effects resulted in a significant phosphaturia and considerable reductions of Mg2+ and Ca2+ excretions. The effects of glucagon at both the whole kidney and the nephron levels are very similar to those previously described for calcitonin. In the absence of an adenylate cyclase system sensitive to glucagon and calcitonin in the rat proximal tubule, and from the analogy of their physiological effects with those elicited by parathyroid hormone, it is suggested that glucagon and calcitonin exert their inhibitory effects on Na and Pi reabsorption in the proximal tubule through another pathway, which could be the phosphoinositide regulatory cascade.
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PMID:Glucagon inhibits water and NaCl transports in the proximal convoluted tubule of the rat kidney. 177 68

There is increasing evidence that persistent depolarization plays a critical role not only in excitation-secretion coupling, but also in the mechanisms linking excitation of neuronal cells to long-term adaptative changes in biosynthesis of neuropeptides. Somatostatin (SRIF) release and synthesis are affected by numerous agents, such as high concentrations of potassium that cause depolarization of cellular membrane. In the present work, we tried to determine whether prolonged exposure to veratridine (VTD) regulates SRIF synthesis. We found that exposure to VTD (100 microM) resulted in the stimulation of total (cell content + media) immunoreactive SRIF (IR-SRIF). This effect was calcium- and sodium-dependent, since it was prevented when verapamil (VPM) 20 microM or tetrodotoxin (TTX) 1 microM were added simultaneously with VTD. Cerebral cortical cells were exposed to high potassium concentrations, and the nature of the IR-SRIF was characterized by high-pressure liquid chromatography (HPLC) or gel filtration. It was evident that chronic exposure to high potassium concentrations modified the elution profile of medium IR-SRIF on HPLC and gel filtration, causing an increase in somatostatin-28 (S-28) and a decrease in somatostatin-14 (S-14). The results indicate that chronic exposure to VTD or high potassium concentration increases immunoreactive somatostatin and augments synthesis of its high-molecular-weight forms. This suggests that chronic membrane depolarization activating sodium and calcium channels initiates the entry of calcium ions, which triggers somatostatin release and causes a depletion of its intracellular stores. The stimulation of somatostatin secretion could be coupled to synthesis of the peptide.
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PMID:Depolarizing influences regulate somatostatin synthesis and processing in cultured cerebral cortical cells. 196 75

The tissue-selective binding of the two principal bioactive forms of somatostatin, somatostatin-14 (SS-14) and somatostatin-28 (SS-28), their ability to modulate cAMP-dependent and -independent regulation of post-receptor events to different degrees and the documentation of specific labelling of SS receptor subtypes with SS-28 but not SS-14 in discrete regions of rat brain suggest the existence of distinct SS-14 and SS-28 binding sites. Receptor binding of SS-14 ligands has been shown to be modulated by nucleotides and ions, but the effect of these agents on SS-28 binding has not been studied. In the present study we investigated the effects of adenine and guanine nucleotides as well as monovalent and divalent cations on rat brain SS receptors quantitated with radioiodinated analogs of SS-14 ([125I-Tyr11]SS14, referred to in this paper as SS-14) and SS-28 ([Leu8, D-Trp22, 125I-Tyr25] SS-28, referred to as LTT* SS-28) in order to determine if distinct receptor sites for SS-14 and SS-28 could be distinguished on the basis of their modulation by nucleotides and ions. GTP as well as ATP exerted a dose-dependent inhibition (over a concentration range of 10(-7)-10(-3) M) of the binding of the two radioligands. The nucleotide inhibition of binding resulted in a decrease the Bmax of the SS receptors, the binding affinity remaining unaltered. GTP (10(-4) M) decreased the Bmax of LTT* SS-28 binding sites to a greater extent than ATP (145 +/- 10 and 228 +/- 16 respectively, compared to control value of 320 +/- 20 pmol mg-1). Under identical conditions GTP was less effective than ATP in reducing the number of T* SS-14 binding sites (Bmax = 227 +/- 8 and 182 +/- 15, respectively, compared to 340 +/- 15 pmol mg-1 in the absence of nucleotides). Monovalent cations inhibited the binding of both radioligands, Li+ and Na+ inhibited the binding of T* SS-14 to a greater extent than K+. The effect of divalent cations on the other hand was varied. At low concentration (2 mM) Mg2+, Ba2+, Mn2+, Ca2+ and Co2+ augmented the binding of both T* SS-14 and LTT* SS-28, while higher than 4 mM Co2+ inhibited binding of both ligands. LTT* SS-28 binding was reduced in the presence of high concentrations of Ba2+ and Mn2+ also. Interestingly Ca2+ at higher than 10 mM preferentially inhibited LTT* SS-28 binding and increased the affinity of SS-14 but not SS-28 for LTT* SS-28 binding sites.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Receptor binding of somatostatin-14 and somatostatin-28 in rat brain: differential modulation by nucleotides and ions. 197 Jan 85

1. The effects of somatostatin on mechanical and electrophysiological responses were studied in guinea-pig atrial muscle preparations and single cells. 2. Somatostatin (greater than or equal to 10(-8) M) decreased the twitch contraction in a concentration-dependent manner in electrically driven left atria and spontaneously beating right atria. However, the beating rate was not affected. 3. The negative inotropic effect of somatostatin was transient. Desensitization to this agent developed slowly during continuous exposure to the peptide. 4. In single atrial cells, somatostatin significantly shortened the action potential duration, but the resting potential and action potential amplitude were not affected. 5. Under whole cell voltage-clamp conditions, somatostatin decreased the calcium inward current without affecting the sodium and potassium currents. 6. These results suggest that somatostatin selectively acts on the calcium channel of guinea-pig atrial cells to reduce the calcium inward current, which in turn gives rise to the negative inotropic effect.
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PMID:Somatostatin decreases the calcium inward current in guinea-pig atria. 197 May 2

Rat brain somatostatin (SRIF) receptors were solubilized in an active form with the detergent 3-[(cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Solubilized SRIF receptors were detected with the stable SRIF analog 125I-MK 678. CHAPS solubilized approximately 30% of membrane-bound SRIF receptors. 125I-MK 678 binding to the solubilized SRIF receptors reached equilibrium by 90 min and dissociated from the receptor with a t1/2 of 60 min. The binding of 125I-MK 678 to the solubilized SRIF receptor was of high affinity and was selective. The characteristics of 125I-MK 678 binding to the solubilized and membrane-bound SRIF receptors were similar. The solubilized brain SRIF receptor specifically bound to a wheat germ agglutinin-Sepharose column, suggesting that it is a glycoprotein. Analysis of the solubilized SRIF receptor by gel exclusion chromatography on an AcA 34 Ultrogel column revealed that its molecular mass is approximately 400 kDa. This mass is probably representative of the receptor complexed with other proteins or molecules. Further characterization of the fractionated 400-kDa species by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting indicated that Gi and Go may be associated with the solubilized SRIF receptor. This is supported by the finding that guanosine-5'-O-(3-thio)triphosphate abolished 125I-MK 678 binding to the solubilized SRIF receptor. Antibodies directed against a synthetic peptide corresponding to a region of the C-terminal of Gia, which specifically immunoprecipitate Gia, immunoprecipitated over 24% of the solubilized SRIF receptor, suggesting that the receptor, in part, is coupled to Gi. These studies describe for the first time the characterization of the solubilized SRIF receptor in an active form. The ability to solubilize the SRIF receptor should allow for further characterization of its physical properties.
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PMID:Solubilization of active somatostatin receptors from rat brain. 197 Oct 88


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