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)

Analytical subcellular fractionation techniques using metrizamide density gradients have been used to investigate the properties of the gut hormone storage granules and the principal organelles from homogenates of normal human jejunal mucosa obtained by peroral mucosal biopsy. The individual hormones, detected by radioimmunoassay, each showed single discrete peaks in the density gradient experiments indicating localisation to single granules each with characteristic modal densities. Thus motilin showed a modal density of 1.15, gastrin 1.16, gastric inhibitory polypeptide (GIP) 1.17, enteroglucagon 1.18 and somatostatin and vasoactive intestinal peptide (VIP) 1.10 g/ml. The following organelles, characterised by their marker enzymes were located in the density gradients; plasma membrane (5'-nucleotidase) brush border (alpha-glucosidase, pH 6.0) mitochondria (particulate malate dehydrogenase), peroxisomes (catalase), lysosomes (N-acetyl-beta-glucosaminidase), endoplasmic reticulum (alpha-glucosidase, pH 8.0), cytosol (lactate dehydrogenase). These studies provide biochemical evidence of the distinct nature of the individual gut hormone storage granules and provide a basis for studying dynamic changes in the granules in response to physiological stimuli and pathological processes.
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PMID:Characterisation of gut hormone storage granules from normal human jejunum using metrizamide density gradients. 730 92

NADPH-diaphorase activity, which has been previously reported to be associated with the enzyme nitric oxide synthase (NOS), was localized cytochemically in the pancreatic islets of normal rats. All islet cells types, i.e. insulin-, glucagon-, somatostatin- and pancreatic polypeptide-immunoreactive cells, expressed NAD-PH-diaphorase histochemical activity, whereas the exocrine tissue was almost negative. In streptozotocin-treated rats, only the surviving non-beta cells in the islet periphery were stained. Isolated beta and non-beta cells also expressed intense NADPH-diaphorase activity. By electron microscopy, the enzyme was localized primarily on membranes of the endoplasmic reticulum and nuclear envelope, as previously reported for neurons. In addition the enzyme activity was found in the cis-region of the Golgi complex. These results suggest that the four types of endocrine cells of the islets of Langerhans may contain the NOS-enzyme and thus constitutively produce nitric oxide.
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PMID:Cytochemical localization of NADPH-diaphorase in the four types of pancreatic islet cell. 752 33

Small peptide hormones (less than 50 amino acids) are synthesized as larger inactive precursors. Work from several laboratories, including our own, has implicated the propeptide of various precursors in mediating intracellular transport and targeting to secretory granules. We previously demonstrated that the proregion of prosomatostatin, one of the simplest peptide hormone precursors, when fused to alpha-globin, enabled the globin polypeptide to be transported to the regulated secretory pathway. To identify sorting motifs in this propeptide, we have now constructed a chimera comprising the somatostatin signal peptide and proregion fused to chloramphenicol acetyl transferase (CAT) and a control protein consisting of the signal peptide fused to CAT, both of which were expressed in rat anterior-pituitary GH3 cells. Both molecules were translocated into the endoplasmic reticulum (ER) efficiently and core-glycosylated on the single cryptic N-linked glycosylation site present in CAT. Surprisingly, the glycosylated propeptide-CAT and signal without CAT were degraded intracellularly with half-lives of 30 min and 90 min, respectively. Based on the kinetics of degradation, temperature sensitivity, and resistance to lysosomotrophic agents, we suggest that degradation occurred in the ER. Our data imply that the pro-region is not an a priori universal sorter, but only directs heterologous peptides to the secretory pathway when the passenger peptide assumes a secretion-competent conformation.
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PMID:Intracellular degradation of prohormone-chloramphenicol-acetyl-transferase chimeras in a pre-lysosomal compartment. 790 39

Alz-50 is a monoclonal antibody raised against ventral forebrain tissue from patients with Alzheimer's disease (AD). It was originally believed that the antigen recognized by Alz-50 was only found in degenerating neurons. However, recent studies indicate that Alz-50 stains neurons in a limited but specific distribution in normal brains throughout life. As the antigen recognized by Alz-50 in normal brains may give some insight into the AD degenerative process, we characterized Alz-50 staining in the normal ovine striatum using immunoblots and immunocytochemistry at the light and electron microscope levels. We then compared the Alz-50 staining pattern with those of NADPH diaphorase histochemistry and immunocytochemistry using antisera against several neuropeptides, Alzheimer-related proteins, and heat-shock proteins. Western blot analysis indicated that the epitope recognized by Alz-50 in the normal sheep brain is on the microtubule-associated protein tau, and preadsorbing Alz-50 with a peptide corresponding to the amino terminus of the tau molecule eliminated staining. Alz-50 labeled a single population of cells in the ovine striatum, the medium aspiny neurons. At the light microscope level, the granular staining pattern closely resembled Alz-50 immunoreactive neurons in the normal human striatum and in cells undergoing early degeneration in AD. Alz-50 immunoreactive neurons stained immunocytochemically with antisera against somatostatin, neuropeptide Y, and histochemically for NADPH diaphorase. These cells were morphologically characterized by smooth dendrites, elaborate local axonal plexuses, and indented nuclei with filamentous inclusions. Ultrastructurally, Alz-50 immunodecorated ribosomes and membranous structures (e.g. vesicles, endoplasmic reticulum), and many boutons which contained Alz-50-positive synaptic vesicles. None of the antisera against other Alzheimer-related proteins, including paired helical filament protein, ubiquitin, beta-amyloid protein, or heat-shock proteins specifically stained the population of cells labelled by Alz-50. Other tau antisera also did not specifically stain these cells. We conclude that Alz-50 recognizes an amino terminal epitope that is exposed on tau proteins within a single, discrete population of neurons in the normal sheep striatum. The presence of this epitope in a normal cell population raises the possibility that the early stages of AD degeneration may involve the activation of a normal cellular pathway that modifies the tau molecule.
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PMID:Alz-50 immunohistochemistry in the normal sheep striatum: a light and electron microscope study. 809 42

We studied the effects of the long-acting somatostatin analogue octreotide (SMS 201-995, Sandoz, Basel, Switzerland) on the morphology of pituitary adenomas in acromegaly. Of the 29 adenomas examined by light microscopy, 16 had been treated pre-operatively with octreotide. The treated adenomas were compared with the untreated adenomas. 14 adenomas were also studied by electron microscopy. In 23 cases we performed in-situ-hybridization for GH-mRNA. Under light microscopy, we found a decrease in amyloid deposits and a higher amount of cell necroses and fibroses after treatment, mainly in the tumors with shrinkage. Tumor shrinkage was diagnosed when the maximal diameter of the adenoma decreased for at least 1/3 during octreotide treatment in NMR examination. Immunohistochemical examinations showed that treated adenomas, especially those with tumor shrinkage, possessed more GH immunoreactive cells, and after in-situ-hybridization we found a higher content of GH-mRNA. On the ultrastructural level, rough endoplasmic reticulum appeared to be increased in treated adenomas. The increase of GH-mRNA and of rough endoplasmic reticulum suggests the likelihood of an increased secretory activity due to a rebound effect after short-term pre-operative omission of octreotide. Other findings are discussed.
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PMID:Effects of octreotide on morphology of pituitary adenomas in acromegaly. 830 23

Pathomorphologic studies were carried out on three cases of bovine diabetes mellitus with clinical signs of polydipsia, polyuria, severe emaciation, glycosuria, persistent hyperglycemia, and decreased glucose tolerance. At necropsy, two animals had atrophy of the pancreas, whereas other visceral organs, including the endocrine organs, showed no significant changes. Microscopically, there was atrophy and reduced numbers of pancreatic islets accompanied by interlobular and interacinar fibrosis and compensatory enlargement of some remaining islets. Lymphocytes were observed commonly around and within atrophic islets and occasionally around and within enlarged islets. Vacuolar degeneration with occasional accumulation of glycogen granules was observed in the beta-cells of these enlarged islets. Immunohistochemical studies of atrophic islets demonstrated complete loss of beta-cells or only a few small beta-cells. There also was a corresponding decrease in the number of cells that stained with anti-glucagon (alpha-cells) or anti-somatostatin (delta-cells) antibodies. The vacuolated cells in the enlarged islets stained strongly with anti-insulin antibody (beta-cells). Ultrastructurally, the majority of cells in the atrophic islets had reduced cytoplasmic volume and few secretory granules, features consistent with alpha-cells. In contrast, enlarged islets that had prominent immunohistochemical staining for insulin (beta-cells) consisted of beta-cells with cytosolic edema, mitochondrial swelling, dilated smooth endoplasmic reticulum, and reduced numbers of or degranulated secretory granules. These pathomorphologic features found in cattle are similar to those found in juvenile-onset insulin-dependent diabetes mellitus in human beings and suggest autoimmune involvement in diabetes.
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PMID:Spontaneous diabetes mellitus in young cattle: histologic, immunohistochemical, and electron microscopic studies of the islets of Langerhans. 844 27

Previous results demonstrate that porcine somatotropes can be separated by density gradient centrifugation into low density (LD) and high density (HD) subpopulations. In rat, two analog somatotrope subpopulations differ morphologically and functionally. In an attempt to determine whether morphological differences were also present within LD and HD porcine somatotropes, we undertook a quantitative electron microscope study of the subcellular organelles of immunoidentified LD and HD somatotropes. In addition, to test for the existence of functional differences, cultures of separated HD and LD subpopulations were treated for 4 h with or without 10 microM GRF-(1-29) and/or 100 microM somatostatin (SRIF), and porcine GH release and intracellular content were evaluated using a homologous enzyme immunoassay. Morphometric results demonstrate that LD somatotropes are smaller in size (P < 0.05) and contain fewer secretory granules (P < 0.05) and more rough endoplasmic reticulum (P < 0.05) than HD somatotropes. In terms of secretion, LD somatotropes showed a classical response; GRF increased GH release 1.7-fold (n = 6; P < 0.05) over the control value, whereas treatment with SRIF alone did not affect basal GH release in this subpopulation, but partially blocked GRF-induced GH release. HD somatotropes responded to GRF with a similar 1.7-fold increase in GH release. However, SRIF administered alone or in combination with GRF exerted a paradoxical stimulatory effect on HD somatotropes (2.15- and 2.12-fold over control value, respectively; n = 6; P < 0.05). These results demonstrate that the porcine somatotrope population is composed of two major subpopulations that display a distinctive pattern of ultrastructural organization and a markedly divergent secretory response to in vitro SRIF treatment.
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PMID:Somatostatin increases growth hormone (GH) secretion in a subpopulation of porcine somatotropes: evidence for functional and morphological heterogeneity among porcine GH-producing cells. 853 3

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

1. Cyclical pressurization of cultured chondrocytes results in increases in cyclic AMP and in the rate of proteoglycan synthesis. Intermittent increases in hydrostatic pressure are also associated with hyperpolarization of chondrocyte cell membranes and activation of Ca(2+)-dependent K(+)-ion channels but the physiological basis for this response to mechanical stimulation is unclear. 2. Experiments have been undertaken to better define the types of ion channels involved and to explore the possibility that the hyperpolarization response associated with cyclical pressurization of chondrocytes follows activation of stretch-activated ion channels. 3. The mean membrane potential of chondrocytes in non-confluent monolayer cell culture rose from -15.3 +/- 0.24 mV to -21.1 +/- 0.28 mV (n = 60, P < 0.0001) after intermittent pressurization (0.33 Hz, 16 kPa, 20 min). 4. Strain gauge measurements showed that cyclical pressurization was associated with strain on the base of the culture plate. The amplitude of the hyperpolarization response was proportional to the microstrain to which cells were subjected. 5. Membrane hyperpolarization did not occur when chondrocytes were subjected to cyclical pressurization in rigid glass culture dishes or plastic dishes positioned in the pressurization chamber so as to avoid bending of the base of the culture dish. 6. Indirect evidence that the hyperpolarization response after intermittent pressure-induced strain was associated with stimulation of stretch-activated ion channels was obtained from experiments with gadolinium, amiloride and hexamethylene amiloride, each of which abolished hyperpolarization. 7. Experiments with apamin, charybdotoxin and iberiotoxin showed that the Ca(2+)-activated K+ channels involved in the hyperpolarization response are apamin-sensitive, charybdotoxin- and iberiotoxin-resistant, low-conductance channels. 8. Somatostatin and cadmium chloride, which block L-type calcium channels, abolished strain-induced chondrocyte hyperpolarization. EGTA, which chelates extracellular Ca2+, reduced the response to 48% of control values, and thapsigargin, which raises intracellular Ca2+ by inhibition of Ca(2+)-ATPase in endoplasmic reticulum, caused hyperpolarization independently with further hyperpolarization after pressure-induced strain. These data indicate that chondrocyte hyperpolarization was dependent on intracellular Ca2+ concentrations. 9. Further work is required to determine whether stretch-activated ion channels shown to be associated with chondrocyte hyperpolarization after cyclical pressure-induced strain are also involved in the signal transduction process that leads to increases in proteoglycan synthesis.
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PMID:Effects of intermittent pressure-induced strain on the electrophysiology of cultured human chondrocytes: evidence for the presence of stretch-activated membrane ion channels. 869 7

Expression of fusion proteins between prepro-alpha-factor and somatostatin (SRIF) in yeast, resulted in the correct processing and secretion of the heterologous 14-amino acid SRIF peptide (1). When the chimeric genes were placed under the control of yeast acid phosphatase (PHO5) promoter, significant amount of an unglycosylated form of the fusion precursor molecule accumulated intracellularly, suggesting disruption of an endoplasmic reticulum-mediated function. We report here that the appearance of the precursor is due to an alteration in the three amino terminal residues of the chimera, i.e., Met-Arg-Phe in native prepro-alpha-factor is changed to Met-Phe-Lys in the hybrids. The unglycosylated precursor represents a population of molecules that are disrupted at an early stage of targeting to or translocation across the endoplasmic reticulum membrane. Our data demonstrate that the N-terminus plays an important role in topogenesis. Furthermore, these results show that translocation and glycosylation can be uncoupled from protein synthesis in vivo, and therefore can be posttranslational events in yeast.
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PMID:Topogenic effect of positively charged N-terminal amino acid in ER translocation of yeast alpha-factor precursor. 885 54


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