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)

Aminopeptidase M (AmM; EC 3.4.11.2) is a membrane-bound peptidase present on renal brush border and vascular plasma membrane. In the present study, AmM, purified from rabbit kidney cortex, produced a single immunoprecipitin line against AmM antisera, hydrolyzed alanyl-, leucyl- and arginyl-beta-naphthylamides at rates of 5.1 +/- 0.5, 3.9 +/- 0.5 and 2.6 +/- 0.3 mumol/min/mg, respectively, exhibited little or no alpha-glutamyl-, aspartyl- or glycyl-prolyl-naphthylamidase activities (less than or equal to 0.14 mumol/min/mg), and was inhibited by o-phenanthroline, amastatin (IC50 = 400 nM) and bestatin (IC50 = 6 microM). The alanyl-naphthylamidase activity of unfractionated rabbit plasma was found to be identical to purified AmM regarding relative rates of hydrolysis of alanyl-, leucyl- and arginyl-naphthylamides (100:79:42), pH optimum, and inhibition profile. In comparative studies with the purified enzyme, immunoreactive AmM accounted for essentially all of the alanyl-2-naphthylamidase activity of rabbit plasma. N-Terminal metabolism of (Met5)enkephalin by purified renal AmM was 3.92 +/- 0.69 mumol/min/mg, followed by somatostatin (1.25 mumol/min/mg), hepta(5-11)substance P (1.14 +/- 0.13 mumol/min/mg), (Asn1)angiotensin II (1.11 +/- 0.06 mumol/min/mg), angiotensin III (0.45 +/- 0.04 mumol/min/mg) and des(Asp1)-angiotensin I (0.36 +/- 0.04 mumol/min/mg). In contrast, substance P, bradykinin, (Sar1,Ala8)angiotensin II and neurokinin analogs containing modified N-termini (e.g. Ac-Arg) were resistant to hydrolysis by AmM. Peptide degradation was optimal at neutral pH and was inhibited by amastatin (IC50 = 200 nM) and bestatin (IC50 = 5 microM). Apparent Km values ranged from 15.7 +/- 0.4 microM for angiotensin III to 102 +/- 2 microM for (Met5)enkephalin. These data support a significant role for vascular and plasma AmM in the metabolism of circulating vasoactive peptides.
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PMID:Metabolism of vasoactive peptides by plasma and purified renal aminopeptidase M. 197 75

A duodenal somatostatinoma was found incidentally in a 60-year-old woman undergoing cholecystectomy. Microscopically, the tumor had a glandular architecture with abundant psammoma bodies. Electron microscopy revealed tumor cells resembling D-cells of the pancreatic islets. Immunohistochemically, there was staining for neuron-specific enolase, chromogranin, and diffuse cytoplasmic positivity for somatostatin only. By immunoelectron microscopy, somatostatin was identified predominantly in lucent membrane-bound secretory granules. X-ray-dispersive microanalysis showed the psammoma bodies contained calcium apatite crystals. This case is compared with other reported cases with a description of cellular localization of somatostatin and development of psammomatous calcification.
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PMID:Duodenal somatostatinoma with psammoma bodies. 256 11

Fourteen hormone-producing gastrointestinal tract tumors were tested for their content of somatostatin (SRIH) receptors, using receptor autoradiography and in vitro binding assay with tumor homogenates. All four gastrinomas tested had high levels of SRIH receptors, as did two of five insulinomas and four of five vasoactive intestinal peptide-producing tumors. Receptor visualization was obtained with two different radioligands, either a SRIH-28 analog, [125I]-[Leu8,D-Trp22,Tyr25]SRIH-28, or a SRIH octapeptide, the [125I]Tyr3 derivative of SMS 201-995 [H-DPhe-Cys-Phe-DTrp-Lys-Thr-Cys-Thr(ol)], [125I]204-090. In both cases receptors were localized over the tumor cell area only. Biochemical and pharmacological analyses of one insulinoma and two vipomas revealed saturable, high affinity binding sites with pharmacological specificity for SRIH. However, differences in receptor affinity of selected SRIH analogs, in particular SRIH-28 and SRIH octapeptides, were found between the insulinomas and the two other tumor types, vipoma and gastrinoma. The presence of SRIH receptors on various hormone-producing gastrointestinal tumors suggests that at least part of the beneficial effects of chronic therapy with SRIH analogs may be mediated through such membrane-bound receptors located on the tumor itself. SRIH receptor measurement may be of prognostic value in assessment of the therapeutic efficacy of SRIH analogs. They may also be of diagnostic value, if used as in vivo markers for the localization of small hormone-producing gastrointestinal tumors or their metastases.
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PMID:Hormone-producing gastrointestinal tumors contain a high density of somatostatin receptors. 282 49

Inhibition of the phosphorylation of the synaptic plasma membrane (SPM) protein B50 by [D-Trp8]-somatostatin in vitro is time-dependent. Increasing the time of incubation of hippocampal synaptic plasma membranes with the peptide from 15 sec to 30 min prior to addition of 7.5 microM [gamma-32P]ATP results in a complete reduction of B50 phosphorylation. Incubation of synaptic plasma membranes for 30 min in the absence of peptide does not alter basal B50 phosphorylation. Neither ACTH nor beta-endorphin produces similar effects--inhibition of B50 phosphorylation by ACTH is maximal at 15 sec and beta-endorphin produces only a small inhibition, even after 30 min. [D-Trp8]-somatostatin is not activating a membrane-bound protease, since maximal inhibition of B50 phosphorylation by the peptide is seen in the presence of leupeptin or bacitracin. Hippocampal synaptic plasma membranes contain protein phosphatase activity. Assays of B50 phosphorylation in synaptic plasma membranes done under conditions that favor either net phosphorylation or dephosphorylation are consistent with inhibition of protein phosphatase activity by [D-Trp8]-somatostatin. This evidence suggests that [D-Trp8]-somatostatin interacts with SPM binding sites in the hippocampus, which may alter the activity of an endogenous protein phosphatase to determine the degree of B50 phosphorylation.
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PMID:Characteristics of [D-Trp8]-somatostatin-sensitive B50 phosphorylation. 287 46

We have previously demonstrated the presence of specific binding sites for somatostatin on plasma membranes from pancreatic acinar cells. In the present study we attempted to characterize the fate of receptor-bound 125I-[Tyr11]somatostatin. Internalization of somatostatin was rapid (reaching a plateau at 20% of the cell-associated specific radioactivity) and temperature dependent. To follow the processing of bound somatostatin, acini were incubated with 125I-[Tyr11]somatostatin at 5 degrees C during 16 h then, after washing, incubated at 37 degrees C for 90 min in fresh medium. Surface-bound somatostatin decreased rapidly, whereas radioactivity increased in the cell interior and the incubation medium. Intracellular and membrane-bound radioactivity was mainly intact 125I-[Tyr11]somatostatin. Degradation occurred at the plasma membrane level and led to iodotyrosine production. After 15 min of incubation, 15% of the initially surface-bound 125I-[Tyr11]somatostatin was compartmentalized within the cell, mainly in the microsomal fraction. After 30 min, a significant increase in radioactivity appeared in the nuclear fraction. These results indicate that the major part of somatostatin cellular degradation takes place at the plasma membrane level. Within the cell, somatostatin is routed to the nucleus via particular fractions sedimenting with microsomal vesicles.
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PMID:Processing of receptor-bound somatostatin: internalization and degradation by pancreatic acini. 288 91

An 8-cm mass in the tail of the pancreas was resected from a 40-year-old man with polyarteritis nodosa. The tumor cells contained abundant, finely granular, eosinophilic cytoplasm arranged in a gyriform pattern that suggested the tumor was an oncocytoma of the endocrine pancreas. Electron microscopy confirmed that the tumor was an oncocytoma by demonstrating tumor cell cytoplasm packed with mitochondria. Ultrastructural and immunocytochemical studies confirmed the neuroendocrine nature of the tumor by demonstrating dense-core, membrane-bound structures consistent with neurosecretory granules and neuron-specific enolase immunoreactivity. No immunoreactivity for insulin, glucagon, gastrin, somatostatin, or pancreatic polypeptide was found. No human chorionic gonadotropin alpha-chain immunoreactivity was detected. The patient is well without evidence of tumor five years after operation. The apparently benign behavior of the pancreatic endocrine oncocytoma reported here is in contrast to the malignant nature of another case reported recently.
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PMID:Benign oncocytic endocrine tumor of the pancreas in a patient with polyarteritis nodosa. 288 5

Rat brain aminopeptidase activity was solubilized from membranes by incubation with thiols. This novel procedure resulted in the release of the same two aminopeptidases (MI and MII) previously shown to be solubilized by the nonionic detergent Triton X-100. The solubilized aminopeptidases MI and MII were resolved by ion-exchange chromatography and further purified by hydroxylapatite chromatography. Aminopeptidase MI was shown to hydrolyze only the beta-naphthylamides of arginine and lysine whereas aminopeptidase MII exhibited a broad specificity with respect to amino acid beta-naphthylamides. Only aminopeptidase MII hydrolyzed Leu-enkephalin at a significant rate, indicating that this enzyme can account for the membrane-bound enkephalin aminopeptidase activity. The enkephalin-degrading aminopeptidase is potently inhibited by opioid (alpha-neo-endorphin and dynorphin) as well as nonopioid (substance P, somatostatin, and angiotensin I) peptides in the range of 0.2-2.0 microM. The regional distribution of aminopeptidases MI and MII in rat brain are rather different, with aminopeptidase MII distribution more closely paralleling the distribution of opiate receptors.
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PMID:Characterization of membrane-bound aminopeptidases from rat brain: identification of the enkephalin-degrading aminopeptidase. 388 43

Medullary thyroid carcinoma (MTC) is a neoplasm derived from thyroidal C cells. This tumor occurs spontaneously in several animal species and is relatively common in certain strains of rats. Descriptive reports of such neoplasms in mice, however, have not been published. From several studies using female BALB/c mice, 3 animals were identified that had thyroid neoplasms histologically compatible with MTC. All three primary neoplasms and a first generation transplant from one of them contained calcitonin. Somatostatin was identified in two of three primary thyroidal neoplasms and in the first-generation transplant. Ultrastructurally, the neoplastic cells of the first-generation transplant contained membrane-bound dense-core granules that resembled those seen in normal mouse C cells. Intracisternal Type A retrovirus particles were also identified in neoplastic cells in this case. Transplantation of one of the neoplasms yielded subcutaneous masses averaging 2 cm in diameter by 3 months following transplantation in the second-generation recipients. These neoplasms resemble MTCs of man, rat, and other species and may prove of value for comparative morphologic and endocrinologic studies of C cell neoplasms and for studies of factors that regulate the synthesis and secretion not only of calcitonin but also of a variety of regulatory peptides, including somatostatin.
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PMID:Medullary thyroid carcinoma in female BALB/c mice. A report of 3 cases with ultrastructural, immunohistochemical, and transplantation data. 613 Jul 3

Twenty unselected breast carcinomas were examined for argyrophilia by the Sevier-Munger stain and for dense-core secretory granules by electron microscopy. All cases were examined for lactalbumin and five cases were also studied for gastrin, insulin, calcitonin, somatostatin, glucagon, ACTH, prolactin, and pancreatic polypeptide by an immunoperoxidase technique; two cases were further analyzed for lactalbumin by ultrastructural immunoperoxidase stain. Focal or diffuse argyrophilia was present in ten cases. Intracytoplasmic lactalbumin was present in seven of these cases, but immunoperoxidase staining for the neuroendocrine hormones was negative. Fine structural examination demonstrated varying numbers of 95 to 450-nm-diameter, round, membrane-bound, dense-core secretory granules in 13 cases. Nine of the granule-containing cases were also argyrophilic, and seven of these contained intracytoplasmic lactalbumin. Both the argyrophilia and the dense-core secretory granules thus correlated with the presence of intracytoplasmic lactalbumin. None of the 20 patients had clinical evidence of carcinoid syndrome or showed evidence of other hormone secretion. Argyrophilia and granular lactalbumin staining in a somewhat similar pattern was found in pregnant and lactating breast controls. Argyrophilia and ultrastructural dense-core granules are common in breast carcinomas and might represent lactational differentiation. These findings do not indicate the presence of a carcinoid tumor because in most of these tumors the secretory granules appear to contain milk protein secretory product rather than neuroendocrine polypeptides, and most argyrophilic tumors do not morphologically or clinically resemble carcinoid tumors.
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PMID:Argyrophilic breast carcinomas: evidence of lactational differentiation. 618 Jun 51

A clonal hamster beta cell line (HIT) was established by simian virus 40 transformation of Syrian hamster pancreatic islet cells. Cytoplasmic insulin was detected in all cells by indirect fluorescent antibody staining, and membrane-bound secretory granules were observed ultrastructurally. Acidified-ethanol extracts of HIT cell cultures contained hamster insulin as determined by radioimmunoassay, radioreceptor assay, and bioassay. One subclone at passage 39 contained 2.6 micrograms of insulin per mg of cell protein. [3H]Leucine-labeled HIT insulin and proinsulin were identical to islet-derived proteins when compared by NaDodSO4/polyacrylamide gel electrophoresis of immunoprecipitates. HIT cell insulin secretion was stimulated by glucose, glucagon, and 3-isobutyl-1-methylxanthine. Insulin secretion at optimal glucose concentration (7.5 mM) was 2.4 milliunits per 10(6) cells per hr. Somatostatin and dexamethasone markedly inhibited HIT insulin secretion. The HIT cell line represents a unique in vitro system for studying beta cell metabolism and insulin biosynthesis.
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PMID:Insulin synthesis in a clonal cell line of simian virus 40-transformed hamster pancreatic beta cells. 627 Jun 73


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