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 binding of 123I-Tyr-3-octreotide (SDZ-204-090; specific activity 1 mCi/nmol), a new somatostatin-receptor binding radiopharmaceutical, to human tumour membrane fractions was evaluated in presence of unlabeled Tyr-3-octreotide and octreotide (SMS-201-995; Sandostatin). Tumour tissue was obtained intraoperatively from 15 patients with different endocrine tumours (insulinoma, carcinoide, phaechromocytoma, hypophysal adenoma) and breast cancer. In equilibrium experiments, membrane fractions (200 micrograms protein/ml) were incubated with increasing concentrations of 123I-Tyr-3-octreotide (0.03-30 nM) in presence or absence of 5 microM of unlabeled agonist. Binding capacities ranged from 1-20 pmol/mg protein (Kd 4-100 nM). The IC50 values (2.5-112 nM versus 0.02-69 nM) were different for the octreotide and Tyr-3-octreotide indicating that octreotide was the better competitor as Tyr-3-octreotide for 123I-Tyr-3-octreotide binding sites. In ductal breast cancer high numbers of in vitro binding sites for the radiolabel were found. In initial clinical studies 123I-Tyr-3-octreotide was i.v.-injected (3 mCi) to 5 acromegaly patients with hypophyseal adenomas. Following rapid uptake by the liver, positive tumour imaging was obtained in 3 patients which correlated to computer tomographic findings. Positive images were obtained just some minutes after injection. Our results support recent data suggesting that the 123I-Tyr-3-octreotide would be a suitable receptor-radiopharmaceutical for the localization of endocrine tumours.
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PMID:Evaluation of somatostatin receptors in human cancer. 166

Control of growth hormone (GH) and prolactin (PRL) release was investigated in hypophysial stalk-transected (HST) and stalk-intact pigs by determining the effects of analogs of GH-releasing factors (GHRF), somatostatin (SRIF), arginine, thyrotropin-releasing hormone, alpha-methyl-rho-tyrosine, and haloperidol. HST and control gilts were challenged with intravenous injections of human pancreatic GHRF(1-40)OH, thyrotropin-releasing hormone, and analogs of rat hypothalamic GHRF. HST animals remained acutely responsive to GHRF by releasing 2-fold greater quantities of GH than seen in controls. This occurred in spite of a 38% reduction in pituitary gland weight and a 32 and 55% decrease in GH concentration and total content. During SRIF infusion, GH remained at similar basal concentrations in HST and control gilts, but increased immediately after stopping SRIF infusion only in the controls. Releasable pituitary GH appears to accumulate during SRIF infusion. GHRF given during SRIF infusion caused a 2-fold greater release of GH than seen in animals receiving only GHRF. Arginine increased (P less than 0.05) GH release in controls, but not in HST gilts, which suggests that it acts through the central nervous system. Basal PRL concentrations were greater (P less than 0.05) in HST gilts than in control gilts. TRH acutely elevated circulating PRL (P less than 0.001) in HST gilts, suggesting that it acts directly on the pituitary gland. Haloperidol, a dopamine receptor antagonist, increased circulating PRL in controls but not in HST animals. alpha-Methyl-rho-tyrosine did not consistently increase circulating PRL, however, suggesting that it did not sufficiently alter turnover rate of the tyrosine hydroxylase pool. The results indicate that the isolated pituitary after HST remains acutely responsive to hypothalamic releasing and inhibiting factors for both GH and PRL release in the pig.
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PMID:Growth hormone and prolactin secretion in hypophysial stalk-transected pigs as affected by growth hormone and prolactin-releasing and inhibiting factors. 167 Dec 98

Analogues of somatostatin (SS) and luteinizing hormone-releasing hormone (LH-RH) activate tyrosine phosphatases in MIA PaCa-2 human pancreatic cancer cell line membranes and inhibit growth. We compared the substrates phosphorylated by epidermal growth factor (EGF) to those dephosphorylated by the SS analogue RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) and [D-Trp6]LH-RH in cancer cell lines such as MIA PaCa-2 (human pancreatic cancer), HCPC (hamster cheek pouch carcinoma), A-549 (human lung cancer), HT-29 (human colon cancer), and R3230AC (breast cancer). EGF phosphorylated proteins of 170, 65, and 60 kDa and analogues of SS and LH-RH promoted the dephosphorylation of these proteins in MIA PaCa-2 and HCPC cell lines. The EGF receptor is 170 kDa. pp60src (60 kDa) is known to be a substrate for EGF receptor. The LH-RH receptor is also 60 kDa. The effects of RC-160 and [D-Trp6]LH-RH were quantitatively different. Examinations of HT-29, A-549, and R3230AC cancer cell lines revealed no phosphorylation by EGF or dephosphorylation by RC-160 and [D-Trp6]LH-RH. In addition to the 170-, 65-, and 60-kDa proteins, 35-kDa proteins were also phosphorylated in some cancer cell lines. This work demonstrates that analogues of SS and LH-RH can reverse the effects of EGF biochemically as well as functionally.
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PMID:Effects of epidermal growth factor and analogues of luteinizing hormone-releasing hormone and somatostatin on phosphorylation and dephosphorylation of tyrosine residues of specific protein substrates in various tumors. 167 42

Glucagon-like peptide-(17-36) amide [GLP-1-(7-36) amide] and peptide tyrosine tyrosine (PYY) are both products of the enteroglucagon cell. To examine the changes occurring during development, we analyzed by RIA the pancreatic concentrations of these two peptides in fetal and neonatal rats. The levels obtained were compared with those of the classical islet hormones, insulin, somatostatin, and glucagon. The total hormone content of the pancreas increased with age for insulin, glucagon, and somatostatin. The amounts of GLP-1-(7-36) amide immunoreactivity (IR) and PYY, however, remained approximately constant in the 3-, 8-, and 30-day-old and adult pancreas. GLP-1-(7-36) amide IR showed only a single peak by gel chromatography, but further analysis by anion exchange chromatography showed that during the fetal period (-18 days) and 3 days postpartum GLP-1-(7-36) amide was the main product, whereas 30 days postpartum and in adult pancreas mainly GLP-1 and an intermediate form were found. Similar analyses of gut extracts revealed that only GLP-1-(7-36) amide is produced during intestinal development. The gut content of GLP-1-(7-36) amide IR and PYY IR increased approximately 100 times between the fetus and the 30-day-old rat. This study reveals a complex and specific regulation of posttranslational processing during maturation for these two peptides.
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PMID:Developmental patterns of glucagon-like peptide-1-(7-36) amide and peptide-YY in rat pancreas and gut. 167 27

The electrochemical activity of catechol- and indoleamines, measured by differential pulse voltammetry (DPV) with specifically electrically pretreated carbon fiber microelectrodes, has been utilized to develop sensitive assays for amine neurotransmitters and metabolites. So far, four oxidation peaks have been recorded in vivo between -200 and +500 mV and are well identified. We now report that by increasing the potential sweep range to +950 mV, a further peak, called Peak 5, was detected at +800 mV in vivo in the striatum of anesthetized rats. Neuropeptides containing tyrosine, tryptophan and/or cysteine appear to be electrochemically active between +600 and +900 mV in vitro in a buffered solution at pH 7.4. The present study investigates the chemical nature of Peak 5 and the possible contribution of electroactive neuropeptides to this in vivo voltammetric signal. Experiments performed in vitro and in vivo with amino acids, neuropeptides, or bacitracin (a potent peptidase inhibitor) support the view that Peak 5 is peptidergic. Furthermore, peripheral administration of cysteamine and intrastriatal injection of specific somatostatin antisera both cause the eventual disappearance of Peak 5, suggesting that somatostatin (which oxidases in vitro at approx +800 mV), or a structurally related peptide, could be the principal component of striatal Peak 5.
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PMID:In vivo voltammetric detection of neuropeptides with micro carbon fiber biosensors: possible selective detection of somatostatin. 167 55

Immunohistochemistry on tissues of larval lampreys, Petromyzon marinus L., was used to determine the distribution of invariant somatostatin-14 (SST-14) and lamprey somatostatin-34 (SST-34) in the brain while antisera against porcine peptide tyrosine tyrosine (PYY), human neuropeptide Y (NPY), anglerfish peptide YG (aPY), salmon glucagon-like peptide (GLP), SST-14, and SST-34 were used in studies of the pancreas and anterior intestine. In the brain, SST-14 is the major form of somatostatin. SST-14- and SST-34-immunoreactive nerve fibers are distributed throughout the telencephalon, diencephalon, and mesencephalon. In the latter region SST-14 immunoreactivity is concentrated in nerve tracts in the nucleus interpeduncularis. Nerve cells within the olfactory bulbs are immunoreactive only to anti-SST-34. Cells immunostained with anti-SST-14 were localized within the ependymal and subependymal layers of the pars ventralis hypothalami and the subependymal layers of the pars dorsalis thalami. SST-14-immunoreactive perikarya are also distributed within the tegmentum mesencephali. Nerve fibers and cells immunoreactive to anti-SST-34 are detected in the pars ventralis hypothalami but these cells do not colocalize SST-14. Pancreatic islets, distributed within the epithelium and in the submucosal connective tissue at the esophageal-intestinal junction, are only immunoreactive to anti-insulin. The antisera revealed three distinct cell types in the intestinal epithelium: type 1 colocalizes aPY, NPY, and PYY; type 2 colocalizes SST-14 and SST-34; and type 3 demonstrates immunoreactivity only to anti-SST-34. Immunoreactivity to anti-GLP is absent.
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PMID:Distribution of two forms of somatostatin and peptides belonging to the pancreatic polypeptide family in tissues of larval lampreys, Petromyzon marinus L.: an immunohistochemical study. 167 24

Ductal pancreatic cancers were induced with N-nitrosobis(2-oxopropyl)amine (BOP) in female Syrian golden hamsters. The animals were then treated for 2 months with 5-fluorouracil (5-FU) and with sustained delivery systems of the LH-RH agonist D-Trp-6-LH-RH antagonist (Ac-D-Nal(2)'-D-Phe(4Cl)2-D-Pal(3)3-D-Cit6,D-Ala10)LH- RH(SB-75) and somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), and with some combinations thereof. In the first experiment, the treatment with D-Trp-6-LH-RH plus 5-FU resulted in 52% inhibition of tumorous pancreas weight, a smaller number of tumor nodules on histology, a marked increase of programmed cell death (apoptosis) and a reduced number of AgNOR (argyrophilic nucleolar organizer region) in tumor cells, as compared with controls. The inhibitory effects of this combination were greater than those obtained with 5-FU and D-Trp-6-LH-RH treatment alone. In the 2nd experiment, a 76% inhibition of tumorous pancreas weight, a significant decrease in the number of tumor nodules, an increased amount of stroma, enhanced apoptosis and decreased AgNORs were observed after therapy with somatostatin analog RC-160 plus 5-FU. Most of these tumor inhibition parameters were superior to those in the group treated with 5-FU alone, and in some cases slightly better than those treated with RC-160 alone. Both LH-RH antagonist SB-75 and somatostatin analog RC-160 caused a significant inhibition of tumors, and their combination had the strongest tumor inhibitory effect, with the best survival of animals, the lowest tumorous pancreas weight and the highest apoptosis index among groups. Our results suggest that the combinations of LH-RH analogs with somatostatin analogs or of either type of analog with 5-FU may be superior to single agents in the therapy of pancreatic cancer.
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PMID:Effect of combination treatment with analogs of luteinizing hormone-releasing hormone (LH-RH) or somatostatin and 5-fluorouracil on pancreatic cancer in hamsters. 167 45

In order to obtain a greater understanding of the role of aminopeptidases in the degradation of peptides and proteins in the nervous system, we have isolated and characterized leucyl aminopeptidase (EC 3.4.11.1) from human cerebral cortex and studied its action on some physiologically important neuropeptides. The enzyme has a low specificity constant for the hydrolysis of Leu-7-amido-4-methylcoumarin (69s-1M-1) but the peptides Tyr-Gly-Gly and Tyr-Gly-Gly-Phe-Leu (Leu5-enkephalin) were much better substrates (specificity constants 8300 and 18050s -1M-1 respectively). Optimum activity for the degradation of Leu-enkephalin was obtained at pH10.5 in the presence of 5mM-Mn++. A sharp drop in specificity constant occurred with increasing chain length in the series Leu-enkephalin, dynorphin 1-8, 1-10 and 1-13, suggesting that the enzyme functions only as an oligopeptidase. Other neuropeptides were poor substrates (cholecystokinin octapeptide, angiotensin-I) or not hydrolysed at all (somatostatin, Arg8-vasopressin).
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PMID:Human brain leucyl aminopeptidase: isolation, characterization and specificity against some neuropeptides. 168 Feb 22

This study demonstrates that somatostatin (SRIF), an endogenous peptide in vestibular nuclei and cerebellum, can produce both a dose-dependent death of Purkinje cells in distinct sagittal regions of cerebellar cortex and vascular infarcts centered selectively in the inferior vestibular nucleus. Alert, adult male rats were given a 5 microliters intracerebroventricular (i.c.v.) bolus of either SRIF alone (20 or 40 micrograms) or a combined dose of SRIF plus either arginine-vasopressin (AVP, 1 micrograms) or an AVP V1 antagonist, (1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)-tyrosine)-arginine 8-vasopressin (mcAVP, 1 micrograms), through an implanted cannula. After a 4-5 day survival, the brains were stained with the cupric-silver selective degeneration method. Two types of dose-dependent lesions were observed in the cerebellar and vestibular nuclei of these animals: degeneration of Purkinje cell responses in the cerebellar cortex and vascular infarcts in vestibular nuclei. These toxic responses were unaffected by application of AVP or mcAVP; hence, they can be attributed to actions of SRIF. The distribution of Purkinje cell degeneration varied with the SRIF dose in different cerebellar regions. Purkinje cell responses in lobules I-III were equivalent at both SRIF doses, and degeneration in the copula pyramis, paraflocculus and paramedian lobule emerged at the higher SRIF dose. Purkinje cells in the medial aspect of lobules IX-X had an intermediate sensitivity to SRIF intoxication. Degenerating Purkinje cells tended to be arranged in parasagittal bands in each region, suggesting parasagittal zonal variations in susceptibility to SRIF intoxication. By contrast, infarctions in the vestibular nuclei only appeared at the higher SRIF dose. These infarcts could be unilateral or bilateral and always involved the inferior vestibular nucleus at the level of the caudal margin of the acoustic tubercle; they often extended into the medial and lateral vestibular nuclei. The infarcts had a necrotic core that was infiltrated by non-neuronal elements. Thus, they appear to reflect a direct or neurally-mediated vascular response to the peptide.
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PMID:Toxic effects of somatostatin in the cerebellum and vestibular nuclei: multiple sites of action. 168 38

Tyr-3-Octreotide is a synthetic derivative of somatostatin and a somatostatin-receptor analogue. The iodine-123-labelled compound localizes somatostatin-receptor-positive tumours. In this paper two patients are reported in whom somatostatin receptors were demonstrated in vitro. In a 60-year-old female with an islet cell carcinoma of the pancreas, multiple liver metastases and previously unrecognized bone metastases in the right acetabulum could be diagnosed as the reason for a persistent hypoglycaemia. In a 60-year-old male an islet cell carcinoma of the pancreas was localized with 123I-Tyr-3-octreotide. The somatostatin receptors were demonstrated in vitro and the tumour was successfully treated with somatostatin. These studies demonstrate that 123I-Tyr-3-octreotide offers the possibility of localizing somatostatin-receptor-positive tumours and their metastases. Moreover the method makes it possible to determine the receptor status of a tumour in vivo.
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PMID:Octreotide scintigraphy localizes somatostatin receptor-positive islet cell carcinomas. 168 23


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