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)

Somatostatin (SRIF) analogues display anti-tumor properties believed to be mediated by specific cell surface somatostatin receptors (SSTR). SSTR subtypes have unique pharmacological properties, including specific GTP-binding protein coupling, ion channel regulation, and cAMP inhibition; therefore, identification of isotypes expressed in tumor cells facilitates current efforts to design potent anti-tumor SRIF analogues. Human and rodent solid, transplantable tumors and tumor cell lines were examined for gene expression of SSTR1, SSTR2 and SSTR3 by reverse transcription of tumor mRNA and subsequent amplification of cDNA by the polymerase chain reaction, using SSTR subtype-specific oligonucleotide primers. SSTR2 mRNA transcripts were observed in all of the tumor cell lines examined. SSTR1 gene expression was seen in several human and rat tumor types, and SSTR3 gene expression observed in two rodent tumor types. SSTR mRNA-positive tumors are expected to possess membrane-bound receptors which could potentially interact with anti-tumor SRIF analogues.
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PMID:Somatostatin receptor subtype gene expression in human and rodent tumors. 851 84

Octreotide (SMS, synthetic miniature somatostatin) effectively alleviates the secretory diarrhea of the malignant carcinoid syndrome. Although SMS inhibits tumor release of serotonin (5HT) and other bioactive agents, it also inhibits the diarrhea in patients who continue to exhibit elevated serum levels of 5HT. This observation suggest that SMS may directly inhibit mediator-stimulated intestinal ion secretion at the mucosal level. To test this hypothesis, intestinal ion secretion was studied in rabbit ileal mucosa mounted in Ussing chambers. Maximal changes in short circuit current (delta Isc) were observed as an indicator of mucosal ion secretion. The application of pathophysiologic concentrations of 5HT (10(-5) M) to the mucosal preps resulted in a delta Isc of 52 +/- 6 microA/cm2. This 5HT-stimulated delta Isc was significantly inhibited by serosal furosemide (10(-3) M) or use of a chloride-depleted medium, indicating that 5HT stimulates electrogenic chloride secretion in the rabbit ileum. Pretreatment with a therapeutic concentration of SMS (10(-8) M) resulted in a significant inhibition of 5HT-stimulated electrogenic Cl- secretion (9 +/- 1 microA/cm2) (P < 0.005). This inhibitory effect of SMS was not seen in tissue pretreated with pertussis toxin. The results of these experiments demonstrate that octreotide inhibits 5HT-stimulated electrogenic chloride secretion at the mucosal level. Additionally this inhibitory effect of octreotide is likely mediated by activation of the inhibitory subunit of membrane-bound GTP-binding regulatory proteins. These results thus provide experimental evidence in support of the ability of SMS to ameliorate the carcinoid diarrhea by a direct effect on stimulated mucosal ion secretion.
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PMID:Octreotide inhibition of serotonin-induced ileal chloride secretion. 853 58

The cellular nature of the giant eosinophilic cells of tuber and of the cells comprising subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis (TS) remains unclear. To assess the characteristics of these lesions, 13 tubers and 6 SEGA were immunohistochemically studied with glial and neuron-associated antigens. In addition to conventional ultrastructure, 6 tubers and 8 SEGA were subjected to immunoelectron microscopic study for glial fibrillary acidic protein (GFAP) and somatostatin. Eosinophilic giant cells of tubers were positive for vimentin (100%), GFAP (77%) and S-100 protein (92%); such cells were also found to a various extent to be reactive for neuron-associated antigens, including neurofilament (NF) proteins (38%) or class III beta-tubulin (77%). SEGA also showed variable immunoreactivity for GFAP (50%) or for S-100 protein (100%); NF epitopes, class III beta-tubulin, and calbindin 28-kD were expressed in 2 (33%), 5 (83%) and 4 (67%) cases, respectively. Cytoplasmic staining for somatostatin (50%), met-enkephalin (50%), 5-hydroxytryptamine (33%), beta-endorphin (33%) and neuropeptide Y (17%) was noted in SEGA, but not in tubers. Ultrastructurally, the giant cells of tubers and the cells of SEGA contained numerous intermediate filaments, frequent lysosomes and occasional rectangular or rhomboid membrane-bound crystalloids exhibiting lamellar periodicity and structural transition to lysosomes. Some SEGA cells showed features suggestive of neuronal differentiation, including stacks of rough endoplasmic reticulum, occasional microtubules and a few dense-core granules. Furthermore, in one case of tuber, a process of a single large cell was seen to be engaged in synapse formation. Intermediate filaments within a few cells of both lesions were decorated by gold particle-labeled GFAP antiserum. Within the tumor cells of SEGA, irregular, non-membrane-bound, electron-lucent areas often contained somatostatin-immunoreactive particles, whereas the latter could not be detected in tuber. The present study provides further evidence of divergent glioneuronal differentiation, both in the giant cells of tubers and the cells of SEGA. The findings of similar cells at different sites, including the subependymal zone, white matter ("heterotopias"), and cortex indirectly supports the idea that these lesions of TS result from a migration abnormality.
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PMID:Tuber and subependymal giant cell astrocytoma associated with tuberous sclerosis: an immunohistochemical, ultrastructural, and immunoelectron and microscopic study. 854 29

Somatostatin (SS) can inhibit growth hormone (GH) secretion from the pituitary and tumor cell proliferation via membrane-bound receptors (SST). Five SST subtypes have been cloned and can be discriminated by specific peptides. In order to evaluate the human tissue distribution of the SSTs, we first used the cross-linking assay with the 125I-SS-14. A cross-linked complex of 57 kDa was detected in a majority (76%) of the surgical biopsies of normal and tumoral tissues examined (N = 222) and in all tested cell lines (N = 20). However, in regard to the organs, the incidence varied from 33% (epiploon metastases) to 100% (colorectal adenocarcinoma, prostate). Additional, minor SS-14 cross-linked complexes were detected in a few samples, suggesting the simultaneous existence of other SST subtypes. In tumor cell lines, the 57-kDa complex was reduced by the SST2-selective SS analogs BIM23014, BIM23060, and BIM23068, and by SS-14 but not by the non-SST2-selective BIM23052 and BIM23056. Its pharmacological profile therefore corresponded to SST2. Northern blot analysis showed one 2.5-kb human SST2 mRNA in these cell lines. We demonstrate that SST2 is detectable in normal and tumoral human tissues and thus represents an SST subtype target for the development of more specific SS analogs.
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PMID:The somatostatin receptor subtype 2 is expressed in normal and tumoral human tissues70. 904 65

The peptide somatostatin (SS) is widely distributed in the mammalian brain where it modulates neuronal activity through interactions with specific membrane-bound receptor subtypes (ssts). Five different ssts were characterized so far (sst1-5) and their selective agonists were developed on the basis of their binding specificity. SS and ssts are transiently expressed in the developing brain, suggesting a functional role of somatostatinergic systems in neuronal maturation. In the present study, we investigated the effects of chronic exposure to either the SS synthetic analogue, SS-14 or octreotide (a long-acting sst2-preferring analogue) on the maturation of SS-immunoreactivity (-ir) in the primary visual cortex of the rat. SS-ir maturation was investigated both by an evaluation of the number of SS-immunoreactive cells and by radioimmunoassay (RIA) to measure the levels of SS in the postnatal visual cortex. In the visual cortex of normal rats, the number of SS-positive cells markedly increased during the second postnatal week and then significantly decreased until the adult value was reached at the third week. Early and repeated intracerebroventricular (i.c.v.) injections of either SS-14 or octreotide prevented the increase in the number of SS-positive cells, with adult values reached at the end of the first postnatal week. Similarly, administration of either SS-14 or octreotide significantly decreased the SS content of the visual cortex, measured at the end of the second postnatal week. These results show that high local concentrations of either SS-14 or octreotide interfere with SS expression in developing cortical neurons in a restricted postnatal period.
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PMID:Chronic exposure to either somatostatin (SS) or octreotide, a long-lasting SS analogue, affects SS expression in the postnatal visual cortex of the rat. 960 76

An autosomal recessive murine mutation, coined "aly/aly" or "alymphoplasia," was recently reported. Homozygotes for aly are defective in both humoral and cell-mediated immune function and have diffuse lymphoid cell infiltration of various tissues, particularly around the conduit ducts of the pancreas and salivary glands. In pilot studies in our laboratories, aly/aly mice were found to have peculiar biliary tract lesions, which were analyzed histologically and immunohistochemically in the present study. The livers of aly/aly mice older than 8 weeks consistently showed a variable lymphoid cell infiltration with lymph follicle formation in portal tracts; intrahepatic biliary epithelial cells showed various types of damage including pseudopyloric gland metaplasia and proliferative changes. In addition, the extrahepatic bile duct and intrahepatic large bile duct were found to contain an acidophilic substance in their epithelial cytoplasm. In the lumen and occasionally in the cytoplasm of these bile ducts, acidophilic crystals were also seen. Ultrastructurally, the intracytoplasmic acidophilic substances consisted of membrane-bound intracytoplasmic inclusions with homogeneous electron density, likely derived from rough endoplasmic reticulum (ER). Immunohistochemically, the cytoplasmic acidophilic substances were simultaneously positive for cystatin C, gastrin, serotonin, and somatostatin. In contrast, the acidophilic crystals did not react with any of these antibodies. These findings suggest that the intracytoplasmic acidophilic substances may contain a precursor of the peptide hormones, possibly because of defective secretion or intracellular transport. We believe that the aly/aly mouse is a useful model for the analysis of biliary metabolic events, and for studies of the interaction of the immune system and biliary destruction.
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PMID:aly/aly mice: a unique model of biliary disease. 962 Mar 19

The tetradecapeptide somatostatin (SRIF) has an inhibitory action on acid secretion in the stomach. It has been suggested that somatostatin may act directly on parietal cells as well as indirectly via histamine-producing cells. A family of high affinity membrane-bound receptors, which are termed sst1-sst5 receptors, mediates the physiological effects of somatostatin. On the basis of functional studies it has been suggested that somatostatin may mediate its actions in the stomach by activation of a somatostatin sst2 receptor type. Two splice variants of the rat sst2 receptor exist, sst2(a) and sst2(b), which differ in length and composition of their intracellular carboxy termini. To date, little information is available on the distribution of the somatostatin sst2(b) receptor in any peripheral tissue. Here we show for the first time the localisation of this receptor isoform in the rat oxyntic mucosa, where the receptor protein was found to be present in parietal cells. This is in contrast to sst2(a) receptor, which was localised to enterochromaffin-like cells and nerve fibres. The differential localisation of the receptor isoforms to two key cell types, parietal cells and enterochromaffin-like cells, may explain how somatostatin inhibits acid secretion by more than one mechanism.
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PMID:Differential distribution of somatostatin sst2 receptor splice variants in rat gastric mucosa. 1039 94

The authors report seven patients with carcinoid tumors of the extrahepatic bile ducts (EHBDs). All patients were women, with an average age at diagnosis of 49.8 years (range, 37-67 yrs). The most common presenting symptom was painless jaundice with or without pruritus. Although one patient had peptic ulcer disease before the onset of obstructive jaundice, none had systemic endocrine manifestations. These neoplasms were most often located in the common bile duct. Grossly, the carcinoid tumors were usually nodular and poorly demarcated, and ranged from 1.1 to 2.7 cm in size. Only one of the neoplasms was polypoid. Microscopically, the tumors had a trabecular or nesting pattern with occasional tubule formation, and were composed of relatively small cells with granular chromatin. All of the neoplasms expressed chromogranin and two expressed synaptophysin. Three expressed serotonin and two of the three were also immunoreactive for pancreatic polypeptide or somatostatin. Two tumors were focally positive for gastrin and one of these two tumors was also positive for serotonin and pancreatic polypeptide. All seven carcinoid tumors showed no immunoreactivity for p53, and assays for p53 loss of heterozygosity analysis were negative in two, suggesting that p53 mutations do not play a role in the pathogenesis of EHBD carcinoids. A mutation in codon 12 of K-ras was found in one carcinoid tumor whereas two of two showed immunoreactivity for Dpc4 protein. In view of the small number of carcinoids studied, the importance of these findings in the pathogenesis of these tumors is unclear. Ultrastructural examination of three of the tumors revealed numerous membrane-bound, round neurosecretory granules. Clinically, these lesions had an indolent course. Even in the presence of lymph node metastases (noted in two patients), all of the patients remained disease free 2 to 11 years (average follow up, 6.6 yrs) after segmental resection or pancreaticoduodenectomy (Whipple's procedure). Because carcinoid tumors of the EHBD are of low malignant potential, they should be separated from the more common adenocarcinomas in this location.
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PMID:Carcinoid tumors of the extrahepatic bile ducts: a study of seven cases. 1107 51

It was previously shown that hormone receptor coupling to voltage-dependent calcium channels in prolactin and growth hormone-producing GH(3) cells was heavily dependent on the specific heterotrimeric combinations of alpha, beta, and gamma subunits of the guanosine triphosphate (GTP)-binding protein family. Consequently, we assessed whether this was also the case for hormonal modulation of the adenylate cyclase (AC) and phospholipase C (PL-C) effector enzymes in GH(3) cells in culture. By employing polyclonal antibodies directed towards C-terminal decapeptides of various alpha subunits in membrane assays, as well as antisense oligonucleotides towards certain beta- and gamma-subunit genes in whole-cell incubations, it was possible to unravel a tentative profile of heterotrimers preferred by some of the seven-transmembrane-stretch receptors in their modulation of AC and PL-C activities. Vasoactive intestinal peptide (VIP) and thyroliberin (TRH) activate membrane-bound AC through alpha(s)beta(2)gamma(2), while somatostatin (SRIH) and dopamine (DA) inhibited the AC through alpha(i2)beta(1)gamma(3). TRH activated membrane-bound PL-C through alpha(q/11)beta(4)gamma(2), while DA inhibition of the PL-C was accomplished via alpha(o)beta(3)gamma(4). Hence, it seems that not only the specificity of alpha subunits determines the coupling between G protein-associated receptors in GH cells, the receptor binding to G proteins also requires certain combinations of beta and gamma subunits.
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PMID:Specific combinations of G-protein subunits discriminate hormonal signalling in rat pituitary (GH(3)) cells in culture. 1130 42

Somatostatin (somatotropin-release inhibitory factor, SRIF) exerts multiple inhibitory actions throughout the central nervous system and the periphery by binding to specific membrane-bound SRIF receptors (sstrs) of which five subtypes (sstr1-5) have now been identified. Individual sstr subtypes have been suggested to mediate selective biological actions of SRIF. Although the adrenal gland is a known target of SRIF action, the sstr subtypes involved in its actions are unclear. This study examined the expression of sstr1-5 in rat adrenal gland by RT-PCR analysis and in situ hybridization (ISH) histochemistry. Using RT-PCR expression combined with Southern blotting, sstr1, -2, -4, and -5 mRNAs were shown in the adrenal gland. ISH histochemistry revealed strong expression of sstr2 mRNA alone localized to the zona glomerulosa of the adrenal cortex and moderate labeling in scattered cells of the adrenal medulla, indicating a possible role for sstr2 in mediating SRIF physiology in this tissue by altering adrenal aldosterone and catecholamine secretion. These data also point to potential roles for sstr subtypes sstr1, -4, and -5 in the adrenal gland.
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PMID:Localization of messenger ribonucleic acids for somatostatin receptor subtypes (sstr1-5) in the rat adrenal gland. 1250 54


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