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)

In this report we describe the identification of a novel cell type in human and canine pancreas using tissue culture techniques. These cells, representing less than 1% of total islet cells, are of a small size (7-10 microm) and highly quiescent. They display a fairly immature morphology, which is characterized by a weakly developed protein synthesis machinery, a few mitochondria and a small number of neuroendocrine granules. These cells, which we have termed "small cells," are usually organized into small clusters, which can be identified within the islets of predominantly small size. They can also be collected as separate structures from preparations of freshly isolated islets. Immunohistochemically, small cells are positive for PDX-1, synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide, alpha-fetaprotein and Bcl-2 and negative for cytokeratin 19 and nestin. Insulin secretion studies demonstrated that these cells secrete insulin in a glucose-responsive fashion, although do not respond to secretagogues such as IBMX and arginine as do mature beta cells. Although this study does not provide evidence of the proliferative and differentiation potential of small cells, their immature morphology, along with a small size and quiescence, let us hypothesize that these cells may serve as progenitors contributing to the islet growth.
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PMID:Identification and characterization of small cells in the adult pancreas: potential progenitor cells? 1224 83

Characterization of both neurochemical phenotype of G protein-coupled receptor (GPCR)-expressing cells and receptor compartmentalization is a prerequisite for the elucidation of receptor functions in the central nervous system. However, it is often prevented by the diffuse and homogeneous distribution of receptor immunoreactivity. This is particularly true for the somatostatin (SRIF) sst2A receptor, which is largely distributed in the mammalian brain. By using this receptor as a model, we investigated whether receptor internalization, a biochemical property shared by numerous GPCRs, would reveal sst2A-expressing cell populations in the rat dorsolateral septum (LSD), a region in which SRIF might play an important modulatory role. Thirty minutes to 1 hour after intracerebroventricular injection of the sst2A receptor agonist octreotide, numerous sst2A-immunoreactive neurons and processes became apparent due to intracytoplasmic accumulation of intensely stained granules. Double-immunolabeling experiments with synaptophysin and MAP2 provided evidence that internalized sst2A receptors are predominantly localized in the somatodendritic compartment. Revealing sst2A receptor-expressing cell bodies permitted to analyze their neurotransmitter content. Quantitative analysis demonstrated an extensive overlap (approximately 85%) between SRIF- and sst2A-expressing neuronal populations. Additionally, numerous SRIF-immunoreactive axon-like terminals were found in close apposition with sst2A-positive cell bodies and dendrites. Taken together, these data suggest that the sst2A receptor is predominantly expressed in LSD neurons as a postsynaptic autoreceptor, thus providing novel neuroanatomic clues to elucidate SRIF neurotransmission in this region. More generally, in vivo agonist-induced internalization appears as a rapid and powerful tool for the neurochemical characterization of GPCR-expressing cell populations in the mammalian brain.
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PMID:Neurochemical characterization of receptor-expressing cell populations by in vivo agonist-induced internalization: insights from the somatostatin sst2A receptor. 1241 43

The CAD cell line originates from catecholaminergic neurons in the central nervous system (CNS) of a simian virus large T antigen transgenic mouse. In the present study, we have immunohistochemically characterized the cell line after differentiation in serum-free medium, using immunofluorescence in combination with confocal laser scanning microscopy (CLSM), immunoblot, and ribonuclease protection assay (RPA). Tyrosine hydroxylase (TH)-, phenylethanolamine-N-methyltransferase (PNMT)-, neuropeptide Y (NPY)-, vesicular monoamine transporter subtype 2-, vasoactive intestinal peptide (VIP)-, somatostatin (SS)-, synaptophysin-, synaptic vesicle protein 2 (SV2)-, and growth-associated protein of 43 (GAP-43)-immunoreactivities (IRs) were present in the cells but not choline acetyltransferase and vesicular acetylcholine transporter. The immunoreactive substances were present in cell bodies in serum-containing medium (SCM), but after serum withdrawal (protein-free medium, PFM) these proteins and peptides were partially shifted into the long process and their varicosities. A few cells cultured in PFM were occasionally found with extremely high TH-immunoreactivity (IR) in cell bodies and processes. Growth-associated protein of 43-immunoreactivity was weak in SCM but was up-regulated (verified with immunoblot) in PFM and concentrated in varicosities along the processes and the distal tips of neurites. The somatostatin receptor subtype 2a (SSR(2(a))) was found in the cytoplasm and the plasma membrane of the CAD-cells. After serum deprivation, all three methods showed that SSR(2(a)) was up-regulated in the cells. Thus, the CAD cell line after differentiation may be suitable for studying dynamics of SSR(2(a)).
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PMID:Adrenergic differentiation and SSR2a receptor expression in CAD-cells cultured in serum-free medium. 1244 Nov 63

Numerous physiological studies as well as in situ hybridization and PCR experiments concur in reporting a role for the sst2A receptor in transducing somatostatin (SRIF) actions in the rat hypothalamus. However, the distribution of this receptor protein is not known within this structure. Regional and cellular localization of the sst2A receptor was therefore examined in the rat hypothalamus using highly sensitive immunohistochemical techniques. In close correspondence with the distribution of SRIF-immunoreactive fibers, numerous hypothalamic areas displayed sst2A receptor immunoreactivity. Receptor labeling was, however, diffusely distributed over the tissue, and few immunopositive cells were apparent. Unraveling the distribution of receptor-expressing cells was achieved through acute in vivo agonist stimulation and subsequent receptor internalization. At the cellular level, double-immunolabeling experiments with synaptophysin and microtubule-associated protein 2 demonstrated that sst2A receptors were predominantly internalized in perikarya and dendrites. Double-labeling experiments with SRIF revealed that 93% of arcuate, but only 18% of periventricular, SRIF-positive neurons expressed internalized receptors. Taken together, these results demonstrate for the first time that the sst2A receptor protein is widely, but selectively, distributed in the hypothalamus, and that postsynaptic sst2A auto- and heteroreceptors are well poised to play an important role in the somatostatinergic regulation of hypothalamic endocrine and metabolic processes.
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PMID:Targeting sst2A receptor-expressing cells in the rat hypothalamus through in vivo agonist stimulation: neuroanatomical evidence for a major role of this subtype in mediating somatostatin functions. 1263 41

Somatostatin (SS) is an inhibitory regulator of secretory and proliferative responses that activates a group of receptors in the plasma membrane termed SSR1-5. SSR2 is one of the most abundant SSR, which also is expressed in high numbers in many neuroendocrine tumor types. Here, we describe a study of the presence and intracellular localization of the spliced variant SSR2(a) and its endogenous ligand SS in the cultured human neuroblastoma (NB) cell line, SH-SY5Y, by immunohistochemistry and confocal laser scanning. The integral neuronal synaptic vesicle membrane proteins synaptophysin (p38) and SV2 were studied, as well as the IR of catecholaminergic and cholinergic markers. RA treatment was used as an inducer of neuronal-like differentiation in our SH-SY5Y cell line. After the treatment, the presence of catecholaminergic markers (including NPY) decreased while the cholinergic markers (including VIP) increased. p38 and SV2 as well as VIP were shifted into the rather long neuritic processes, indicating efficient intracellular transport. The SSR2(a) protein was significantly increased by RA treatment, but only minor increases in mRNA for this receptor protein could be seen. No subcellular co-localization between p38/SV2 and the cytoplasmic granular receptor material was demonstrated. The SSR2(a) receptor ligand SS was found to be present not only in the cytoplasm but also in the nucleus, and more strongly so after RA treatment. The possible reason for this may be that this peptide, like other small peptides, may serve as transcription factor, or cofactor.
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PMID:SSR2(a) receptor expression and adrenergic/cholinergic characteristics in differentiated SH-SY5Y cells. 1267 30

Somatostatin is a potent antiproliferative signal in both tumoral and normal mammalian cells, and altered somatostatin receptor (sst) expression is associated with carcinogenesis in human tissues. In this study, two normal and three tumoral human pineal glands were analyzed using the reverse transcriptase-polymerase chain reaction (RT-PCR) for the presence of mRNA coding for the five different somatostatin receptors (sst1-sst5). Pineal parenchymal tumor (PPT) differentiation was confirmed by immunohistochemical detection of neuroendocrine markers (synaptophysin, neurofilaments, and chromogranin A). The presence of mRNA coding for c-myc, a proto-oncogene, and for tryptophan hydroxylase (TPOH), serotonin N-acetyltransferase (NAT), and hydroxyindole-O-methyltransferase (HIOMT), enzymes of the melatonin pathway, was also analyzed by RT-PCR. Only the tumoral tissues contained c-myc mRNA. All five tissues contained TPOH, NAT, and HIOMT mRNA, the levels of HIOMT mRNA being lower in PPT than in the normal pineal gland, suggesting that PPT retain the ability to synthesize melatonin. All tissues contained sst1, sst2, and sst3 transcripts, but not sst4, while small amounts of sst5 mRNA were only found in normal pineal glands. Real-time PCR, performed only with the most abundant subtpe sst2, evidenced an about sixfold higher level in in normal pineal glands. These results demonstrate the presence of somatostatin receptors in the human pineal gland, as described in other species, and point to a differential expression of the sst2 and sst5 subtypes associated with carcinogenesis.
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PMID:Differential somatostatin receptor subtype expression in human normal pineal gland and pineal parenchymal tumors. 1270 86

A golden yellow polyp was detected in the gallbladder of a 64-year-old man who presented with epigastric pain. The lesion was composed of clear polygonal cells arranged in a trabecular and glandular pattern. The tumor invaded through the wall into the perimuscular subserosal layer. Immunohistochemical stains showed that neoplastic cells were positive for chromogranin A, synaptophysin, somatostatin, gastrin, and pancreatic polypeptide and negative for glucagon, serotonin, insulin, S100 protein, and inhibin. This tumor resembles the recently described clear cell endocrine tumors of the gallbladder and pancreas that are associated with von Hippel-Lindau disease. Our patient, however, had neither personal nor family history indicative of von Hippel-Lindau disease. Furthermore, published accounts of clear cell endocrine tumors in von Hippel-Lindau disease describe immunoreactivity for inhibin; the current case was negative for the disease. There may be a subtype of clear cell carcinoid tumor not associated with von Hippel-Lindau disease, which is characterized by its lack of immunoreactivity against inhibin.
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PMID:Clear cell carcinoid tumor of the gallbladder. A case without von Hippel-Lindau disease. 1274 4

Carcinoid tumors belong to the family of neuroendocrine tumors, which are usually slow growing with distinct biological and clinical characteristics. The incidence of these tumors is approximately 2.5 in 100,000 people per year. The former classification system of foregut, midgut and hindgut tumors is still used in clinical routine, although there is a new World Health Organization classification. Determination of the histopathology of carcinoid tumors is of utmost importance and involves specific immunohistochemical staining for chromogranin A, synaptophysin, serotonin and gastrin. Proliferation capacity measured by Ki67 is used to guide forthcoming medical treatment. Localization procedures include computerized tomography, ultrasound, magnetic resonance imaging, somatostatin receptor scintigraphy and positron emission tomography. Surgery remains the cornerstone of treatment and provides the only chance of a cure. Other cytoreductive procedures include radiofrequency ablation, laser treatment and chemoembolization. Biological treatment includes cytotoxic agents, such as somatostatin analogs and interferon-alpha, which should be applied in slow-growing neoplasms. Combination regimens including cisplatin, etoposide, streptozotocin and 5-fluorouracil should be reserved for treatment of highly proliferating tumors. Future therapy of carcinoid tumors will be based on the specific tumor biology and treatment will be customized for each individual patient. New therapies, such as antiangiogenic agents and new, long-acting somatostatin analogs, together with further development of tumor-targeted treatments, will come into clinical use in the near future.
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PMID:Diagnosis and treatment of carcinoid tumors. 1468 8

Many disturbances in electrolyte and hormonal balance in the body induced by functional impairment of renal parenchyma may affect the activity of amine precursor uptake and decarboxylation (APUD) cells, which constitute a very important link in the regulation of homeostasis. The aim of the present study was the morphological, immunohistochemical and ultrastructural estimation of enteroendocrine cells in the stomach of uremic rats. Fragments of gastric pylorus were collected 1, 2 and 4 weeks after nephrectomy. Paraffin embedded sections were stained with H + E and by silver impregnation. For identification of neuroendocrine cells, immunohistochemical reactions were performed using specific antibodies against somatostatin, synaptophysin, neuron-specific enolase and anti-calcitonin gene related peptide. The analysis showed an increased number of APUD cells in the stomach of uremic rats compared to control rats, which may be a morphological expression of their hyperfunction in the functional impairment of renal parenchyma. These results suggest that chronic renal failure can modulate the secretory processes of APUD cells.
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PMID:Immunohistochemical and electron-microscopic identification of neuroendocrine cells in the stomach of uremic rats. 1522 20

The aim of the present study was to characterise immunohistochemically and ultrastructurally the neuroendocrine cells in the pulmonary systems of uraemic rats. Pieces of lung and trachea were collected 1, 2 and 4 weeks after nephrectomy. Paraffin-embedded sections were stained with H+E and by silver impregnation. For the identification of neuroendocrine cells immunohistochemical reactions were performed with the use of specific antibodies against calcitonin (CT), somatostatin (SOM), synaptophysin (SYN), neuron-specific enolase (NSE) and calcitonin gene-related peptide (CGRP). For electron microscopy, ultrathin sections were used. The analysis showed an increased number of both the solitary neuroendocrine cells and of neuroepithelial bodies in uraemic rats when compared to control animals.
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PMID:Immunohistochemical and electron-microscopical identification of neuroendocrine cells in the respiratory tract of rats with experimental uraemia. 1523 84


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