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 effects on pancreatic responses of highly potent cyclic hexapeptide (cyclo (N-Me-Ala-Phe-D-Trp-Lys-Thr-Phe)) (Veber analog) and octapeptide analogs of somatostatin such as D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol (SMS 201-995), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) have been compared with somatostatin tetradecapeptide (SS-14) and atropine. The parameters evaluated were pancreatic responses to secretin and meat feeding in conscious dogs with chronic pancreatic fistula and amylase release from the dispersed pancreatic acini. The analogs were administered intravenously or intraduodenally. The cyclic hexapeptide and octapeptide analogs, given iv in graded doses against a constant background stimulation with secretin, produced similar and dose-dependent inhibition of pancreatic HCO3- and protein secretion. Analogs RC-121, RC-160, and the Veber analog were about two to four times more active than SS-14 in suppressing HCO3- secretion and equipotent in reducing protein secretion, but SMS 201-995 was only about half as potent as somatostatin in inhibiting HCO3-. RC-160 was effective in inhibiting secretin-induced protein secretion at lower doses than other analogs. In tests with feeding, SMS 201-995, the Veber analog, RC-121, and RC-160 were more potent inhibitors of exocrine pancreatic secretion of HCO3- and protein and exhibited more prolonged inhibitory effects than SS-14. The Veber analog, RC-121, and RC-160 were also more effective after intraduodenal administration. Atropine also caused significant inhibition of both HCO3- and protein responses to secretin and meal feeding. All four analogs decreased the postprandial insulin and pancreatic polypeptide release to a similar degree as SS-14. Neither SS-14 nor the analogs tested significantly affected basal or caerulein-, gastrin-, secretin-, or bethanechol-stimulated amylase release from the dispersed canine pancreatic acini. Atropine reduced amylase release induced by bethanechol, but not that stimulated by caerulein, gastrin, or secretin. This indicated that the analogs, as somatostatin, are ineffective as secretory inhibitors in vitro. We conclude that cyclic hexapeptide and octapeptide analogs are more potent and longer acting inhibitors of pancreatic secretion than somatostatin-14 in vivo.
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PMID:Comparison of somatostatin and its highly potent hexa- and octapeptide analogs on exocrine and endocrine pancreatic secretion. 244 2

Rat and human alpha- and beta-calcitonin gene-related peptide (CGRP), in the concentration range 1-100 nM, produced sustained relaxations of longitudinal muscle from the rat fundus and guinea pig gastric corpus. The peptides were equipotent and equally effective. Tetrodotoxin, adrenoceptor and purine receptor antagonists, somatostatin, apamin and Tyr-rat alpha-CGRP-(28-37) peptide did not modify the action of the CGRP peptides. The CGRP-induced responses were inhibited by verapamil and potentiated by Bay K-8644. Incubation of the tissues with indomethacin markedly reduced the magnitude of the CGRP- and adrenaline-induced relaxations, but their responsiveness was restored by addition of prostaglandins E1, E2 and F2 alpha in concentrations that alone did not affect the motility of the indomethacin-treated strips. It is suggested that an inhibitory receptor for CGRP on gastric smooth muscle cells is linked to calcium channels and may be activated or sensitized by endogenous prostaglandins.
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PMID:Calcitonin gene-related peptides relax guinea pig and rat gastric smooth muscle. 247 Jun

Galanin was infused intravenously in 8 healthy volunteers at a dose of 40 pmol/kg.min for 1 h to investigate the pharmacologic effects of this peptide on postprandial gastrointestinal motility and gut peptide release in humans. Galanin strongly inhibited gastrointestinal motility. Gastric emptying was significantly delayed, with the time taken to empty 50% of the gastric contents increasing from 59.0 +/- 4.8 min (control infusion) to 99.3 +/- 4.7 min (galanin infusion). Mouth-to-cecum transit time increased from 67.5 +/- 6.9 to 126.3 +/- 18.5 min. Galanin potently suppressed the initial postprandial rise in plasma concentrations of glucose, insulin, peptide tyrosine tyrosine, neurotensin, enteroglucagon, pancreatic glucagon, somatostatin, and pancreatic polypeptide, but did not change gastric inhibitory polypeptide, motilin, peptide histidine methionine, and gastrin concentrations compared with control. The results indicate that an infusion of galanin has potent effects on the gastrointestinal tract in humans. The changes in motor activity in particular suggest that the local galaninergic innervation could have an important physiologic role in the control of human gastrointestinal propulsive motor activity.
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PMID:Inhibitory effect of galanin on postprandial gastrointestinal motility and gut hormone release in humans. 247 97

Galanin, a 29 amino acid peptide, inhibits insulin and somatostatin secretion from the isolated, perfused dog pancreas. To assess the nature of the influences of galanin on the endocrine pancreas, we examined the effects of porcine galanin and six different galanin analogues at the equimolar concentration of 1 nmol/l on the hormone release from the isolated, perfused dog pancreas. It was found that galanin2-29 (by 75 +/- 4%), like the native galanin1-29 (by 90 +/- 3%) potently inhibited insulin secretion (p less than 0.001). In contrast, galanin3-29 did not significantly affect insulin secretion. This indicates that removal of the two N-terminal amino acids markedly reduces the potency of galanin. Also, the replacement of the amino acid number 2 (Trp) by Tyr or Phe was followed by a loss of the insulin lowering effect of galanin at this dose level. Likewise, galanin10-29 had no significant effect on insulin secretion. In contrast, the C-terminally deleted galanin1-15 significantly inhibited insulin secretion (by 24 +/- 5%; p less than 0.01), though with a lower potency than did native galanin (p less than 0.05). Consequently, the C-terminal end of galanin is also of importance for the effect. Somatostatin secretion was inhibited by galanin (p less than 0.001), but not by any of the other investigated peptides. Glucagon secretion was not affected by galanin. It is concluded that the two N-terminal amino acids of galanin are essential for the inhibitory action on the insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:On the nature of the galanin action on the endocrine pancreas: studies with six galanin fragments in the perfused dog pancreas. 247 81

A series of cyclic, conformationally constrained photolabile peptides related to the enkephalins and to somatostatin were designed and synthesized in an effort to develop highly selective and potent peptides for the delta and mu opioid receptors. The following new peptides were prepared and tested for their delta opioid receptor potency and selectivity in the guinea pig ileum assay, the mouse vas deferens assay, and the rat brain binding assay: H-Tyr-D-Pen-Gly-p-NH2Phe-D-Pen-OH (1, [p-NH2Phe4]DPDPE) and H-Tyr-D-Pen-Gly-p-N3Phe-D-Pen-OH (2, [p-N3Phe4]-DPDPE). The following new peptides were prepared and tested for their mu opioid receptor potency and selectivity in the same assays: H-D-Phe-Cys-p-NH2Phe-D-Trp-Lys-Thr-Pen-Thr-NH2 (3, [p-NH2Phe3]CTP) and D-Phe-Cys-p-N3Phe-D-Trp-Lys-Thr-Pen-Thr-NH2 (4, [p-N3Phe3]CTP). The delta selective photoaffinity peptide 2 displayed both high affinity (IC50 = 9.5 nM) and good selectivity (IC50 mu/IC50 delta = 1053) as an agonist at delta opioid receptors in bioassays, and 2 also displayed moderate affinity (33 nM) and excellent selectivity (IC50 mu/IC50 delta = 110) for rat brain delta opioid receptors. The mu selective photoaffinity peptide 4 displayed very weak affinity (8% contraction at 300 nM) at mu opioid receptors in bioassays, but good affinity (IC50 = 48.6 nM) and excellent selectivity (IC50 delta/IC50 mu = 412) for the rat brain mu opioid receptors. These conformationally constrained cyclic photoaffinity peptides may be useful tools to investigate the pharmacology of delta and mu opioid receptors.
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PMID:Synthesis of highly mu and delta opioid receptor selective peptides containing a photoaffinity group. 253 26

Female Syrian golden hamsters with N-nitrosobis(2-oxopropyl)amine (BOP)-induced ductal pancreatic cancers were treated with long-acting microcapsular preparations of the 6-D-tryptophan analog of luteinizing hormone-releasing hormone [( D-Trp6]LH-RH), releasing 25 micrograms/day; the somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), liberating 15 micrograms/day; and the combination of these two peptides. Therapy with analogs was initiated 24 weeks after initial administration of BOP. These treatments resulted in significantly better survival of all animals as compared to BOP controls; body weights of surviving peptide-treated animals were significantly higher than those of the BOP controls. All 15 BOP-control animals had pancreatic cancers. In the group treated with RC-160 four hamsters were free of tumors, whereas therapy with [D-Trp6]LH-RH resulted in seven tumor-free animals, and combination of RC-160 and [D-Trp6]LH-RH resulted in eight tumor-free animals from groups of 15. Only preblastomatous lesions were found in these animals. Average tumor weight of animals in all peptide-treated groups, sacrificed 60 days after beginning the peptide treatment, was significantly lower than that of BOP controls. No significant differences were seen between the various peptide-treated groups. Histologically, analog-treated tumors of hamsters showed striking regressive changes characteristic of programmed cell death (apoptosis). This apoptosis presumably resulted from hormonal effects on tumor cells from prolonged treatment with these analogs of hypothalamic hormones. Our present data confirm the beneficial effect of long-acting microcapsules of [D-Trp6]LH-RH and RC-160 on pancreatic carcinoma and suggest a mode of action for these peptides. The feasibility of applying this treatment with analogs of hypothalamic hormones to human pancreatic carcinoma can be envisioned from these studies.
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PMID:Programmed cell death (apoptosis) in pancreatic cancers of hamsters after treatment with analogs of both luteinizing hormone-releasing hormone and somatostatin. 256 4

Antitumoral effects of the agonist of luteinizing hormone-releasing hormone (D-Trp-6-LH-RH) and the somatostatin analog RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) on chemically induced ductal pancreatic adenocarcinomas were studied. The tumors were induced in female Syrian golden hamsters by weekly s.c. injections of N-nitrosobis(2-oxopropyl)amine at a dose of 10 mg/kg b.w. for 6 weeks. 18 weeks after the last injection, the peptides in controlled-release microcapsule formulations were administered s.c. The animals received the following therapies: Group 1 (N = 15), vehicle only; Group 2 (N = 13), D-Trp-6-LH-RH microcapsules releasing 25 micrograms/day injected s.c. once a month; Group 3 (N = 14), RC-160 microcapsules, liberating 25 micrograms/day administered s.c. every 15 days; Group 4 (N = 14), the combination of D-Trp-6-LH-RH plus RC-160 microcapsules. The experiment was terminated on the 80th day when all hamsters in the control group were dead, but in the treated Groups 2, 3, and 4, we observed 71, 77, and 86% of survival rate, respectively. In addition to the prolongation of survival, the combination treatment resulted in a significant decrease in the tumorous pancreatic weight, increase in the body weight of the animals, reduction in ascites from 100 to 8.3% and regressive histological changes in 67% of the specimens. Our findings suggest that somatostatin analogues and D-Trp-6-LH-RH could be considered for the development of hormonal therapy for pancreatic cancer.
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PMID:Treatment of N-nitrosobis(2-oxopropyl)amine-induced pancreatic cancer in Syrian golden hamsters with D-Trp-6-LH-RH and somatostatin analogue RC-160 microcapsules. 256 12

Several analogues of somatostatin were examined in the Mia PaCa-2 human pancreatic cancer cell line for their ability to promote tyrosine phosphatase activity affecting the receptors for the epidermal growth factor. The inhibition of growth of the Mia PaCa-2 cells in culture was also evaluated to determine the mechanism of action of somatostatin analogues and their relative effectiveness in inhibiting cancer growth. Of the analogues tested D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) caused the greatest stimulation of tyrosine phosphatase activity. Analogue D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) had less effect but was more potent than somatostatin-14. Analogue D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr(ol) (SMS 201-995) produced no significant dephosphorylation. The analogues displayed the same order of activity in assays on growth inhibition of Mia PaCa-2 cells in cultures. Analogue (SMS-201-995) caused virtually no tyrosine phosphatase stimulation or growth inhibition in this cancer cell line, although it possesses a much higher antisecretory activity than somatostatin-14 in normal tissues. These observations indicate that somatostatin and some of its analogues can act as growth inhibitors in cancer cells through the activation of tyrosine phosphatase. These data reinforce the view that somatostatin analogue RC-160 and related compounds could be used for treatment of pancreatic cancer.
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PMID:Somatostatin analogues inhibit growth of pancreatic cancer by stimulating tyrosine phosphatase. 256 78

To determine the effect in normal subjects of small variations of insulin and glucagon on plasma aminoacids concentrations we suppressed endocrine pancreas secretion with somatostatin and measured aminoacids levels during a sequential insulin infusion in the absence (control test, low glucagon level) or in the presence (normal glucagon concentration) of a replacement glucagon infusion. Insulin infusion rates were 0.05, 0.09, 0.15 and 0.30 mU.kg-1.min-1 during the control test and 0.09, 0.15, 0.30 and 0.40 mU.kg-1.min-1 during the replacement test. During the control test, glucagon decreased (p less than 0.01) and insulin levels were successively 8.2 +/- 0.4, 10.1 +/- 0.7, 11.9 +/- 0.14 and 18.5 +/- 0.8 mU.l-1. The only effect on insulin was to decrease branched-chain aminoacids (BCAA). BCAA were inversely related to insulinemia (p less than 0.01). A significant decrease was obtained for an insulin level of 11.9 +/- 0.4 mU.l-1, a value intermediate between those decreasing glycerol (10.1 +/- 0.7 mU.l-1) and stimulating total body glucose uptake (18.5 +/- 0.8 mU.l-1). During the test with glucagon replacement glucagon was maintained at its initial value. Insulin levels were successively 8.3 +/- 0.3, 11.9 +/- 0.3, 19.7 +/- 0.6 and 26.7 +/- 0.5 mU.l-1. Insulin decreased always BCAA but also threonine, proline, tyrosine, methionine and total aminoacid levels. BCAA were always inversely related to insulin levels (p less than 0.01) but the slope of the relationship was modified and more insulin was needed to decrease BCAA concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of small variations in insulin and glucagon levels on plasma aminoacids concentrations. 256 20

A series of six synthetic octapeptides, structurally related to somatostatin, demonstrate high affinity and selectivity for mu opioid receptors in radioligand binding assays. The compounds, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (CTP), D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), D-tetrahydroisoquinoline carboxylic acid (D-Tic)-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (D-Tic-CTP), D-Tic-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (D-Tic-CTOP) and D-Tic-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (D-Tic-CTAP), were tested in vitro and in vivo for agonist and antagonist potency and selectivity. In vitro bioassays included the guinea pig ileum, mouse vas deferens and rabbit vas deferens. In vivo tests included hotplate antinociception and gastrointestinal transit inhibition, performed in mice. In vitro, all six derivatives were competitive, highly selective mu antagonists (pA2 values from 6.4-7.9). The compounds demonstrated varying degrees of intrinsic agonist activity especially in the mouse vas deferens, the least active being CTAP and D-Tic-CTAP, which showed no mu or kappa agonist actions, and delta activity only at very high (greater than 3 microM) concentrations. In vivo, none of these compounds showed antinociceptive actions when administered i.c.v. in mice. All were competitive mu antagonists in the hotplate antinociception test.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Novel peptidic mu opioid antagonists: pharmacologic characterization in vitro and in vivo. 256 79


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