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)

We studied the effect of somatostatin on contractile responses to electrical field stimulation (EFS) in isolated ferret tracheal segments. Somatostatin (up to 10(-5) M) did not change resting tension, but it potentiated the contractile response to EFS dose dependently, with a maximum effect at 10(-6) M. Thus, at a concentration of 10(-6) M, somatostatin significantly decreased the mean log of EFS frequency producing 50% of maximum contraction from a control value of 0.52 +/- 0.07 to 0.24 +/- 0.06 (SE) Hz (P less than 0.01). The potentiating effect of somatostatin (10(-6) M) was not inhibited by hexamethonium, indomethacin, BW755C, pyrilamine, methysergide, or D,Pro2,D,Trp7,9-SP, but it was inhibited by atropine or by the somatostatin antagonist cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)]. In contrast to EFS-induced contraction, contractions produced by acetylcholine (10(-9) to 10(-3) M) were not affected by somatostatin at a concentration of 10(-6) M. These results suggest that somatostatin potentiates contractions produced by EFS via presynaptic cholinergic mechanisms and probably through a specific somatostatin receptor.
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PMID:Somatostatin potentiates cholinergic neurotransmission in ferret trachea. 257 91

A series of heptapeptide somatostatin (SRIF) analogs containing mercaptopropionic acid (Mpa) and based on the parent structure Mpa-Tyr-[D]Trp-Lys-Val-Cys-Thr-NH2 were synthesized by solid-phase methodologies and assayed for their effects on rat growth hormone (GH) secretion and their ability to displace [125I]Tyr11-SRIF bound to various tissues in vitro. Structural modifications consisted primarily of aromatic substitutions for Thr. All analogs were less potent than SRIF in inhibiting GH secretion in vitro from 4-day primary cultures of rat pituitary cells (0.04-21% that of SRIF). Higher GH inhibitory potencies were observed in an acute 15 min in vivo potency assay probably reflecting increases in plasma half-life of the analogs as compared to native SRIF. All analogs had extremely low binding affinity for rat cerebral cortex (0.05-4% that of SRIF), while binding potency for rat pancreas ranged from 3-130% of SRIF. Several analogs exhibited enhanced binding to human small cell lung carcinoma cells (SCLC; NCI-H69) as compared to SRIF. One of these, containing Phe at the C-terminus, exhibited an affinity 3.5 X greater than SRIF itself and was further tested for possible effects on the proliferation of SCLC and rat pancreatic tumor cells (AR42J) in vitro. The proliferation of both tumor types was inhibited 32 and 60%, respectively (p less than 0.01). The data suggest that SRIF and certain analogs may have a direct action on proliferating tumors independent of endocrine effects and that the anti-tumor activity of SRIF analogs can be further dissociated from the other actions of native SRIF, thereby providing for potentially more selective therapeutic analogs.
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PMID:Novel heptapeptide somatostatin analog displays anti-tumor activity independent of effects on growth hormone secretion. 257 97

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

A new strain, named WRT cells, has been generated from primary cultures of rat thyroids. The primary culture was grown in Coon's modified Ham's F12 medium with 5% calf serum, insulin, hydrocortisone, transferrin, somatostatin, glycyl-L-histidyl-L-lysine and thyrotropin (TSH). On the basis of the following facts, the WRT cell strain, cloned from the primary culture, was considered 'normal': the cells are euploid, not carcinogenic, not able to grow in soft agar, and show contact inhibition. Their differentiated functions consist of the ability to synthesize thyroglobulin and to take up iodide, and they have a TSH-dependent adenylate cyclase system. TSH increases cellular adenosine 3',5'-cyclic monophosphate (cAMP) levels and [3H]thymidine incorporation in WRT cells from a concentration similar to that active on another clonal rat cell line (FRTL-5), even though the cell replication appears to be differently regulated in the two cell strains. In fact, the WRT cell doubling time is 42 h and they are also able to grow in the absence of TSH, though more slowly. In the same conditions, FRTL-5 cells have a population doubling time of 38 h, but they are not able to grow in the absence of TSH. When the effect of the other growth factors of the medium was studied, insulin appears to be a growth stimulus by itself, while it is only a facilitative step for TSH action in FRTL-5 cells. WRT cells, unlike FRTL-5 cells, can grow with a population doubling time of 80 h, when cultured for prolonged periods in a medium with a low serum concentration (0.5%), but containing insulin plus TSH. In conclusion, the WRT cell strain is a new and interesting experimental model for studying growth factors at the level of the thyroid, especially for their mechanism of action on the TSH receptor.
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PMID:Insulin stimulates cell growth of a new strain of differentiated rat thyroid cells. 282 50

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


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