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 cytoprotective effect of a highly potent somatostatin (SRIF) analog, RC-121 (H-D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2), was examined in the absolute ethanol-induced gastric erosion model in rat. This analog diminished the degree of gastric erosion by 50-55% when administered in i.p. doses of 2 x 10(-10)-10(-8) g/100 g body weight, or in oral doses of 10(-8)-2 x 10(-7) g/100 body weight. The orally active, highly potent SRIF analogs may be useful as therapeutic agents in the treatment of human peptic ulcer.
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PMID:Protective effect of an orally administered, highly potent somatostatin analog (RC-121) against absolute ethanol-induced hemorrhagic erosions of the rat gastric mucosa. 273 41

Fourteen hormone-producing gastrointestinal tract tumors were tested for their content of somatostatin (SRIH) receptors, using receptor autoradiography and in vitro binding assay with tumor homogenates. All four gastrinomas tested had high levels of SRIH receptors, as did two of five insulinomas and four of five vasoactive intestinal peptide-producing tumors. Receptor visualization was obtained with two different radioligands, either a SRIH-28 analog, [125I]-[Leu8,D-Trp22,Tyr25]SRIH-28, or a SRIH octapeptide, the [125I]Tyr3 derivative of SMS 201-995 [H-DPhe-Cys-Phe-DTrp-Lys-Thr-Cys-Thr(ol)], [125I]204-090. In both cases receptors were localized over the tumor cell area only. Biochemical and pharmacological analyses of one insulinoma and two vipomas revealed saturable, high affinity binding sites with pharmacological specificity for SRIH. However, differences in receptor affinity of selected SRIH analogs, in particular SRIH-28 and SRIH octapeptides, were found between the insulinomas and the two other tumor types, vipoma and gastrinoma. The presence of SRIH receptors on various hormone-producing gastrointestinal tumors suggests that at least part of the beneficial effects of chronic therapy with SRIH analogs may be mediated through such membrane-bound receptors located on the tumor itself. SRIH receptor measurement may be of prognostic value in assessment of the therapeutic efficacy of SRIH analogs. They may also be of diagnostic value, if used as in vivo markers for the localization of small hormone-producing gastrointestinal tumors or their metastases.
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PMID:Hormone-producing gastrointestinal tumors contain a high density of somatostatin receptors. 282 49

The effects of a cyclic hexapeptide analog of somatostatin, [cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe)] (cyclo-SS), administered intravenously (iv) or instilled into the duodenum (id) on the pancreatic response to endogenous (meal and duodenal acidification) and exogenous (secretin, CCK) stimulants were compared in five dogs with esophageal, gastric, and pancreatic fistulae. Cyclo-SS given iv in graded doses against a constant background stimulation with secretin caused a similar and dose-dependent inhibition of pancreatic HCO3 and protein secretion being about twice as potent as somatostatin-14 (SS-14). Cyclo-SS, whether applied topically to the duodenal mucosa in a dose of 1 microgram/kg or given iv at a dose of 0.5 microgram/kg-hr, resulted in a similar inhibition of pancreatic secretion induced by feeding a meat meal, sham-feeding, duodenal acidification, or infusion of secretin or CCK. The inhibition of pancreatic secretion by cyclo-SS was due in part to direct inhibitory action on the exocrine pancreas as well as to the suppression of the release of secretin, insulin, and pancreatic polypeptide. It is concluded that cyclo-SS is a more potent inhibitor of pancreatic secretion than SS-14 and that it is active when administered both parenterally and intraduodenally.
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PMID:Effects of cyclic hexapeptide analog of somatostatin on pancreatic secretion in dogs. 285 53

A series of cyclic, conformationally restricted analogs of somatostatin have been prepared and tested for their ability to inhibit the binding of [3H]naloxone and [D-Ala2, D-Leu5] [3H]enkephalin to rat brain membranes. The most potent analog, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 where Pen is penicillamine in [D-Phe5, Cys6, Tyr7, D-Trp8, Pen11]somatostatin-(5-12)-octapeptide amide, exhibited high affinity for mu-opiate receptors (IC50 value of [3H]naloxone = 3.5 nM), being 7800 times more potent than somatostatin. The cyclic octapeptide also displayed high mu-opiate receptor selectivity with an IC50 [( D-Ala2,D-Leu5]enkephalin)/IC50 (naloxone) ratio of 271. The high affinity and selectivity of the somatostatin analog for mu-opiate receptors may be of use in examining the physiological role(s) of the mu-opiate receptor.
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PMID:Conformationally restricted analogs of somatostatin with high mu-opiate receptor specificity. 285 88

A novel 28-residue somatostatin (SS) has been isolated from anglerfish pancreatic islets and characterized by complete Edman degradation, peptide mapping, and amino acid analysis. The primary structure of this anglerfish SS-28 (aSS-28) containing hydroxylysine (Hyl) was established to be H-Ser-Val-Asp-Ser-Thr-Asn-Asn-Leu-Pro-Pro-Arg-Glu-Arg-Lys-Ala-Gly-Cys- Lys-Asn-Phe-Tyr-Trp-Hyl-Gly-Phe-Thr-Ser-Cys-OH. This sequence (with the exception of hydroxylysine-23, which is replaced by lysine) is identical to the sequence of the COOH-terminal 28 residues of prepro-SS II predicted on the basis of cDNA analysis [Hobart, P., Crawford, R., Shen, L., Pictet, R. & Rutter, W. J. (1980) Nature (London) 288, 137-141]. This is the first instance in which hydroxylysine (to date characteristically observed in collagen or collagen-like structures) has been found in a potential regulatory peptide. Chromatographic characterization of peptides, radiolabeled in islet culture, revealed that aSS-28 contained 10-12% of the radioactivity incorporated into the 8000- to 1000-dalton SS-like polypeptides, whereas 88-90% of this radioactivity was detected in anglerfish SS-14. It appears probable that aSS-28 represents the predominant primary cleavage product derived from prepro-SS II by cleavage at the COOH-terminal side of a single arginine. Based on knowledge of the collagen biosynthesis, it is speculated that hydroxylation may take place as an early post-translational event.
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PMID:Processing of an anglerfish somatostatin precursor to a hydroxylysine-containing somatostatin 28. 285 89

The effect of long-term administration of analogs of luteinizing hormone-releasing hormone (LH-RH) and somatostatin on the growth of the growth hormone (GH)- and prolactin (PRL)-secreting rat pituitary GH3 tumor was investigated. Daily administration of [D-Trp6]LH-RH (50 micrograms/day), early after inoculation of the GH3 tumor, inhibited tumor growth by more than 90% as compared to controls. Similarly, in two experiments, a single once-a-month injection of long-acting [D-Trp6]LH-RH microcapsules (in a dose calculated to release about 25 micrograms/day for 30 days) inhibited the growth of GH3 pituitary tumor by more than 50% 6 or 13 wk after transplantation, when the tumors were fully developed. Serum GH and PRL levels also were reduced markedly by treatment with [D-Trp6]LH-RH. On the other hand, the administration of an antagonistic analog of LH-RH, N-Ac-[D-Phe(4Cl)1,2, D-Trp3, D-Arg6, D-Ala10]LH-RH, did not significantly reduce the growth of this tumor, and the treatment with two different analogs of somatostatin, cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) and D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr NH2, appeared to enhance it. These results are in agreement with previous findings of growth inhibition of 7315a pituitary tumors with different hormone-secreting characteristics by agonistic analogs of LH-RH. The collective data from experimental work with rat pituitary tumor models support the contention that the use of [D-Trp6]LH-RH might be considered for the treatment of some patients with pituitary tumors who failed to respond to conventional therapy.
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PMID:Inhibition of growth of a prolactin and growth hormone-secreting pituitary tumor in rats by D-tryptophan-6 analog of luteinizing hormone-releasing hormone. 285 96

Somatostatin inhibits the uptake of phallotoxins and of cholic acid in isolated liver cells in a concentration-dependent manner. The inhibition is independent on the preincubation period and fully reversed by switching to a somatostatin-free buffer. Concentrations needed for 50% inhibition decreased 30-80-fold when somatostatin was modified by variation of its amino acid sequence. Some cyclic hexa- or penta-peptides inhibited both kinds of transport more strongly as the original (14 amino acid) somatostatin did. Three of the analogs showed a 2-3-fold higher potency than the others. The most potent compound (cyclo (Phe-Thr-Lys-Trp-Phe-D-Pro) 1 was studied in detail. The IC50 for the initial uptake of phallotoxin (6 microM) or of cholate (6 microM) was 1.5 or 3 microM, respectively. 1 inhibited the uptake of cholate in a competitive manner. The inhibition was independent on the preincubation time, but in contrast to somatostatin not fully reversible after a preincubation of 35 min. Somatostatin as well as its analogs prevented binding of isothiocyanatobenzamido [3H]cholate (an affinity label of the cholate transporter) to isolated plasma membranes from rat liver. The transport inhibition of cholate uptake is unlikely to be a hormonal effect of somatostatin, because the concentrations needed are approx. 1000-fold higher than circulating levels; however, it is apparently possible to increase the inhibitory potency on the tested transport system by modification of the sequence without increase of the well-known hormonal effects (Designing Activity and Receptor-Selectivity in Cyclic Peptide Hormone Analogs, Kessler, H., 18th Ervag Conference, Brussels, 1983).
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PMID:Modified somatostatins as inhibitors of a multispecific transport system for bile acids and phallotoxins in isolated hepatocytes. 285 22

Somatostatin receptors in rat brain, pituitary, and pancreas were labeled with two radioiodinated analogs of somatostatins 14 and 28. Two cyclic analogs of somatostatin, SMS201-995 and cyclo(Ala-Cys-Phe-D-Trp-Lys-Thr-Cys), showed biphasic displacement of binding to somatostatin receptors by these radioligands. In contrast, all other somatostatin analogs, including somatostatin-14, competed for the receptor sites with monophasic displacement of radioligand receptor binding. Thus two types of somatostatin receptors were identified. It was found that the pituitary and pancreas have predominantly one type of somatostatin receptor whereas the brain has both, and that different regions of the brain have various proportions of the two types. These findings suggest methods to characterize other types of somatostatin receptors subserving somatostatin's diverse physiological functions, including a potential role in cognitive function and extrapyramidal motor system control.
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PMID:Two types of somatostatin receptors differentiated by cyclic somatostatin analogs. 285 17

The effects in vivo of physiologic increases in insulin and amino acids on myocardial amino acid balance were evaluated in conscious dogs. Arterial and coronary sinus concentrations of amino acids and coronary blood flow were measured during a 30-min basal and a 100-min experimental period employing three protocols: euglycemic insulin clamp (plasma insulin equaled 70 +/- 11 microU/ml, n = 6); euglycemic insulin clamp during amino acid infusion (plasma insulin equaled 89 +/- 12 microU/ml, n = 6); and suppression of insulin with somatostatin during amino acid infusion (plasma insulin equaled 15 +/- 4 microU/ml, n = 6). Basally, only leucine and isoleucine were removed significantly by myocardium (net branched chain amino acid [BCAA] uptake equaled 0.5 +/- 0.2 mumol/min), while glycine, alanine, and glutamine were released. Glutamine demonstrated the highest net myocardial production (1.6 +/- 0.2 mumol/min). No net exchange was seen for valine, phenylalanine, tyrosine, cysteine, methionine, glutamate, asparagine, serine, threonine, taurine, and aspartate. In group I, hyperinsulinemia caused a decline of all plasma amino acids except alanine; alanine balance switched from release to an uptake of 0.6 +/- 0.4 mumol/min (P less than 0.05), while the myocardial balance of other amino acids was unchanged. In group II, amino acid concentrations rose, and were accompanied by a marked rise in myocardial BCAA uptake (0.4 +/- 0.1-2.6 +/- 0.3 mumol/min, P less than 0.001). Uptake of alanine was again stimulated (0.9 +/- 0.3 mumol/min, P less than 0.01), while glutamine production was unchanged (1.3 +/- 0.4 vs. 1.6 +/- 0.3 mumol/min). In group III, there was a 4-5-fold increase in the plasma concentration of the infused amino acids, accompanied by marked stimulation in uptake of only BCAA (6.8 +/- 0.7 mumol/min). Myocardial glutamine production was unchanged (1.9 +/- 0.4-1.3 +/- 0.7 mumol/min). Within the three experimental groups there were highly significant linear correlations between myocardial uptake and arterial concentration of leucine, isoleucine, valine, and total BCAA (r = 0.98, 0.98, 0.92, and 0.97, respectively); P less than 0.001 for each). In vivo, BCAA are the principal amino acids taken up by the myocardium basally and during amino acid infusion. Plasma BCAA concentration and not insulin determines the rate of myocardial BCAA uptake. Insulin stimulates myocardial alanine uptake. Neither insulin nor amino acid infusion alters myocardial glutamine release.
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PMID:Regulation of myocardial amino acid balance in the conscious dog. 285

Cyclic octapeptide analogues of somatostatin (SS) like SMS 201-995 [H-(D) Phe-Cys-Phe-(D) Trp-Lys-Thr-Cys-Thr(ol)] or its Tyr3-derivative 204-090, displaced [125I-Tyr11]-SS 100% from pancreatic membranes but only 62-75% from brain membranes; the remaining sites were displaced by SS. These data indicate that some mini-somatostatins bind to a subpopulation of SS receptors in rat brain. The iodinated Tyr3-derivative (125I-204-090) can be considered a selective radioligand for one rat brain SS receptor subpopulation: It shows saturable and high affinity binding (KD = 0.29 nM; Bmax = 350 fmoles/mg protein) to rat cortex. The pharmacological properties of 125I-204-090 binding sites are similar to those of [125I-Tyr11]-SS sites. Distribution of these sites correspond to SS receptor-rich areas such as cortex, hippocampus, striatum, pituitary, pancreatic beta-cell. SS as well as SMS 201-995 bind to these sites with high affinity. The stability and high specific vs non-specific binding ratio makes 204-090 a radioligand of choice to measure this SS receptor subpopulation in CNS but also the SS receptors in pituitary and pancreas.
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PMID:New specific radioligand for one subpopulation of brain somatostatin receptors. 285 10


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