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)

1. The biochemical specificity and duration of action of a single 5 mg subcutaneous dose of des-AA1,2,4,5,12,13-D-Trp8-somatostatin were evaluated in eight patients with symptomatic pancreatic endocrine tumours. 2. There was a reduction by more than 50% for at least 10 h in plasma concentrations of growth hormone, glucagon, gastrin and motilin and for 4--5 h in plasma insulin, pancreatic polypeptide, gastric inhibitory polypeptide and enteroglucagon. 3. This study shows that this octapeptide analogue of somatostatin, like somatostatin itself, lacks specificity in the hormones it suppresses. However, its prolonged duration of action against several hormones when given subcutaneously suggests that it may be of therapeutic use in a number of disease states where excessive plasma concentrations of one or more of these hormones occur.
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PMID:Effect of a long-acting octapeptide analogue of somatostatin on growth hormone and pancreatic and gastrointestinal hormones in man. 611 53

The potency and specificity of somatostatin (SS) and four of its analogs were compared in seven patients with pancreatic endocrine tumors. The analogs tested were [D-Trp8]-SS, [D-Trp8, D-Cys14]-SS, Des-Asn5-[D-Trp8, D-Ser13]-SS, and Des (AA)1,2,4,5,12,13, [D-Trp8]-SS, and they did not show selective effects on the suppression of basal concentrations of GH, insulin, glucagon, pancreatic polypeptide, gastrin, gastric inhibitory peptide, motilin, enteroglucagon, or neurotensin. The observation that the potency of these analogs is similar to that of the parent molecule throws considerable light on the structure/activity relationship of the somatostatin molecule. Des-AA1,2,4,5,12,13, [D-Trp8]-Ss has been reported to have a prolonged action when administered sc. When administered iv, however, this octapeptide analog ws not long acting, suggesting that the prolonged action seen in the previous study was a result of delayed uptake from the injection site. An increment in plasma SS concentrations of 19 +/- 3 pmol/liter suppressed basal concentrations of GH, insulin, glucagon, and several gastrointestinal hormones by more than 50%, suggesting that even small changes in plasma SS levels may be physiologically important.
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PMID:The effect of somatostatin analogs on secretion of growth, pancreatic, and gastrointestinal hormones in man. 611 21

The gross behavior induced by centrally administered bombesin in rats was compared to that elicited by ACTH-(1-24) and the somatostatin analog, des AA1,2,4,5,12,13[D-Trp8]-somatostatin (ODT8-SS). Bombesin (0.001-1 microgram, ICV) caused dose-related excessive scratching which was qualitatively different from that associated with the other two groom-inducing agents. Bombesin-induced grooming was not markedly affected by behaviorally nondepressant doses of haloperidol, morphine, naloxone or neurotensin. Bombesin was active in genetically hypotrichotic (essentially furless) rats; and, again in such animals, even after numbing the area caudal to the shoulders with lidocaine. Tolerance and cross-tolerance studies with bombesin and ODT8-SS indicated that they produce scratching through different mechanisms. Bombesin caused scratching when injected directly into the periaqueductal gray, but not when administered intravenously. Neither hypophysectomy nor adrenalectomy markedly affected bombesin-induced grooming. This behavior appears to be initiated in the central nervous system and is produced independently of the pituitary-adrenal axis.
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PMID:Studies on bombesin-induced grooming in rats. 614 1

In the present study the effects of intracerebroventricularly [icv] administered somatostatin [linear and cyclic], somatostatin3-6, somatostatin7-10 and des AA1,2,4,5,12,13 [D-Trp8] somatostatin [ODT8-SS] were investigated on electroconvulsive shock [ECS]-induced retrograde amnesia in rats. The ECS significantly decreased the foot shock-induced avoidance latency, and thus caused retrograde amnesia. Somatostatin [linear and cyclic] in a dose of 0.6 nM had no action on the ECS-induced retrograde amnesia, while in doses of 3 nM and [cyclic only] 6 nM it significantly prevented it. Somatostatin3-6, somatostatin7-10 and ODT8-SS in doses of 0.6, 3 and 6 nM had no effect on the ECS-induced amnesia. These results indicate that the whole sequence of the original somatostatin molecule is needed to block the ECS-caused retrograde amnesia.
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PMID:The effects of somatostatin, its fragments and an analog on electroconvulsive shock-induced amnesia in rats. 614 72

The inhibitory and stimulatory effects of somatostatin analogues on growth hormone secretion have been studied in the sheep. Plasma immunoreactive growth hormone (GH) was stimulated by the iv administration of the antilipolytic compound 3,5-dimethylpyrazole and was followed by infusion of somatostatin (SRIF) and analogues into the carotid artery. The analogues D-trp8-D-cys14-SRIF, des-AA1,2,4,5,12D-trp8-D-cys-14SRIF, and SRIF-Wy 40793 were shown to cause a dose-dependent suppression of plasma GH, followed by a significant rise ("rebound") on terminating the infusion. In general, the greater the suppression, the greater the rebound. A significant correlation between the rebound increase in plasma GH and dose of both SRIF and des-AA1,2,4,5,12D-trp8-cys14-SRIF was demonstrated (p less than 0.01 and p less than 0.001, respectively). This analogue and Wy-40793 showed a significantly greater rebound than did SRIF following 50% suppression of the GH response (p less than 0.01 and p less than 0.05, respectively). Although two analogues were shown to be significantly more potent than SRIF (p less than 0.01), in this sheep bioassay the duration of action did not appear to be longer than that of the native hormone for any of the three analogues.
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PMID:Suppression and stimulation of growth hormone release in sheep by somatostatin analogs. 615 52

The effect of somatostatin (SRIF) analogs on the secretion of radioimmunoassayable SRIF (SRIF-LI) was studied in the model system of fetal rat hypothalamus cells maintained in long-term, primary dispersed culture. These experiments exploited the biologic activity of certain synthetic SRIFs which cross-react poorly in our standard RIA for SRIF. Carbachol-stimulated SRIF-LI secretion was suppressed by [DTrp8]-SRIF-14, [DTrp22]-SRIF-28 and the octapeptide, des-AA1,2,4,5,12,13[DTrp8]-SRIF. Effective concentrations of synthetic analogs were at or below 1 nM. des-Trp8-SRIF-14, an analog inactive in all other SRIF biological assays, was similarly ineffective in this assay system at doses up to 10 nM. Following removal of peptide by washing, peptide-treated and control cells responded similarly to depolarization with high potassium buffer. The data demonstrate a direct action of SRIF analogs on the hypothalamus to suppress SRIF-LI release and are consistent with the possibility that an endogenous peptide participates in 'ultrashortloop' negative feedback control of its own secretion in the intact animal.
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PMID:Somatostatin analogs inhibit somatostatin secretion from cultured hypothalamus cells. 615 Nov 26

The in vivo fate of a long acting somatostatin analogue [des-AA1,2,3,4,13,14,D-Trp8,Gaba12]-somatostatin has been studied in the rat using biochemical and autoradiographic techniques. The analogue has a longer plasma half-life than somatostatin. This is due to its greater metabolic stability which renders it resistant to enzymic attack in the tissues. The primary route of elimination is by biliary excretion following clearance from the circulation by the liver. Evidence of enterohepatic circulation was found, but only to a very limited extent. When administered s.c., high plasma concentrations of intact peptide persist for a period of hours due to slow release from a stable depot at the injection site.
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PMID:Pharmacokinetics, distribution and elimination of a synthetic octapeptide analogue of somatostatin in the rat. 615 65

Somatostatin (SRIF) induces its biological actions by interacting with a family of five recently cloned receptors. SRIF receptor subtype, SSTR1, has high affinity for SRIF, but no ligand has been available that selectively binds to this receptor. Desamino acid(1,2,5) [DTryptophan8, N-p-isopropl-4-aminomethyl-l-phenylalanine9]SRIF(des-AA1,2,5 [DT rp8, IAmp9]SRIF inhibits the binding of [125ITyr11]SRIF to the cloned human SSTR1 with an affinity of 1.8+0.7nM, but does not bind to the other cloned SRIF receptors. des-AA1,5[125ITyr2,DTrp8,IAmp9]SRIF bound selectively, potently and saturably to SSTR1 with a Kd of 0.5 + 0.1 nM and a maximal binding density of 226 +/- 56 fmol/mg of protein. The binding of des-AA1,5[125ITyr2,DTrp8,IAmp9]SRIF to SSTR1 was potently inhibited by SRIF, [DTrp8]SRIF, des-AA1,2,5[DTrp8,IAmp9,DSer13]SRIF and SRIF 28 with K, values of 0.7+0.3, 0.2+0.2, 4.3+0.7 and 0.6+0.1 nM, respectively. SRIF analogs that selectively bind to SSTR2 and SSTR5 were impotent in displacing des-AA1,5[125ITyr2,DTrp8,IAmp9]SRIF from human SSTR1. des-AA1,5[125ITyr2,DTrp8,IAmp9]SRIF binding to SSTR1 expressed in COS-7 cells was reduced by GTPgS, and this effect was prevented by pertussis toxin treatment. In contrast, the binding of[125ITyr11]SRIF to SSTR1 was not affected by these treatments. These findings indicate that des-AA1,5[125ITyr2,DTrp8,IAmp9]SRIF may bind to SSTR1 in a defferent manner than SRIF. des-AA1,2,5[DTrp8,IAmp9]SRIF and its tyrosine analog are the first ligands that selectively bind to SSTR1 with high affinity and should be useful in localizing and determining the functional properties of this receptor.
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PMID:Development of a selective agonist at the somatostatin receptor subtype sstr1. 878 39

Somatostatin and its analogs act in the brain to influence gastric acid secretion. Five different somatostatin receptor subtypes have been characterized (sst1 to sst5). We studied the influence of somatostatin (0.18-0.6 nmol/rat) and selective sst2, sst3 and sst5 receptor ligands on basal gastric acid secretion in conscious rats equipped with chronic gastric and intracerebroventricular (i.c.v.) cannulae. Somatostatin-14 (0.36 nmol/rat), the sst2, sst3 and sst5 receptor agonist, Des-AA1,2,4,5,12,13-[D-Tryp8,D-Cys14]somatostatin (SMS 201-995) (0.18-0.36 nmol/rat) and the sst5 receptor agonist, BIM-23052, (0.8-1.2 nmol/rat) injected i.c.v. inhibited gastric acid secretion. Maximal inhibition reaching 42%, 60% and 42% was induced by somatostatin-14 (0.36 nmol/rat), SMS 201-995 (0.18 nmol/rat) and BIM-23052 (0.8 nmol/rat) respectively. The sst2 receptor agonist, DC 32-87 (0.2-0.8 nmol/rat) and sst3 receptor agonist, BIM-23056 (0.2-1.2 nmol/rat), did not modify gastric acid secretion, except the sst3 receptor agonist at 0.4 nmol/rat which increased acid output at 20 min post-injection. The sst2 receptor agonists (0.4 nmol/rat) co-injected i.c.v. with a subthreshold dose of sst5 (0.4 nmol/rat) inhibited gastric acid secretion. These results show that i.c.v. injection of somatostatin-14 inhibits basal gastric acid secretion in conscious rats through an action on sst5 receptor subtype which can be potentiated by sst2 receptor subtype.
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PMID:Intracerebroventricular injection of somatostatin sst5 receptor agonist inhibits gastric acid secretion in rats. 883 51

In pregnancy, the human placenta GH acts as a growth-promoting hormone and appears to be the main stimulator of insulin-like growth factor I (IGF-I) secretion. In a woman with a TSH-secreting macroadenoma, successful treatment with the somatostatin analog octreotide was conducted during the first month and the second half of pregnancy without side-effects on placental and fetal development. As observed in normal pregnancy, both serum placental GH and IGF-I levels increased throughout pregnancy and dropped sharply after delivery. In placental membranes from both treated and healthy untreated patients, we demonstrated the presence of high affinity binding sites for somatostatin-14 (Kd, 4.6 and 5.3 nmol/L; binding capacity, 1.53 and 1.35 pmol/mg protein, respectively). These receptors displayed low affinity for octreotide (IC50, 1.2-2 mumol/L), suggesting the presence of SST1 and/or SST4 receptors. We found that messenger ribonucleic acids of these two subtypes were expressed in both human placental tissue and purified human cytotrophoblast cells. Finally, the SST1-selective analog, des-AA1,2,5[D-Trp8,IAmp9]S-14 had low affinity for placental somatostatin receptors. These results argue in favor of the presence of the SST4 subtype in human placenta. At the doses administered, octreotide did not bind to placental somatostatin receptors. Our results may explain the absence of changes in both human placental GH and IGF-I concentrations that we observed during octreotide treatment.
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PMID:Expression of somatostatin receptor SST4 in human placenta and absence of octreotide effect on human placental growth hormone concentration during pregnancy. 936 May 39


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