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)

These studies were performed to examine the axoplasmic transport of somatostatin (SS) in the cervical vagus nerve of the rat. As a preliminary step, the immunoreactive SS (IR-SS) obtained from extracts of the vagal nodose ganglion and the vagus nerve was subjected to chromatographic analysis. On a Bio-Gel P-10 column, 92% of the nodose ganglion IR-SS and 98% of the vagal IR-SS coeluted with synthetic SS-14. The remaining immunoreactivity in both areas coeluted with synthetic SS-28. Vagal IR-SS demonstrated migratory characteristics identical to those of synthetic SS-14 on high performance liquid chromatography. A larger molecular weight form of IR-SS, which may correspond to prosomatostatin, was not identified in either site. When the vagus nerve was ligated distal to the nodose ganglion, the content of IR-SS increased in a time-dependent manner in the 3-mm segment of nerve proximal to the ligature. No increase in IR-SS was observed in an equal segment of nerve distal to the ligation or in the unligated contralateral nerve. Twenty-four hours after the ligation, the content of IR-SS (picograms per 3 mm; mean +/- SD) was: proximal segment, 33.9 +/- 9.6; distal segment, 3.4 +/- 3.0; and contralateral nerve, 1.7 +/- 0.7. The apparent transport velocity of IR-SS was estimated to be 2.1 +/- 1.5 mm/h. A variety of experimental approaches were used to characterize the mechanisms underlying the transport process and to define the anatomical sites of origin of the transported peptide. The application of colchicine to the vagus nerve resulted in an accumulation of IR-SS above the area which was not significantly different from that obtained after nerve ligation. When the vagus nerve was crushed above the nodose ganglion, the accumulation of IR-SS in the proximal segment was reduced by 50%, although the IR-SS content in the nodose ganglion and in the intervening nerve segments was unchanged by this procedure. The induction of a chemical sympathectomy with guanethidine had no effect on the accumulation of IR-SS. The administration of capsaicin during the neonatal period or in adult life had no effect on the transport of IR-SS, but greatly decreased the transport of substance P.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Studies of the axoplasmic transport of somatostatin in the vagus nerve of the rat. 620 Mar 14

The axoplasmic transport of somatostatin (SS) and substance P (SP) in the cervical vagus nerve was studied in the rat, guinea pig and cat. In preliminary studies, neuropeptide immunoreactivity (IR-SS and IR-SP) was evaluated in extracts of nodose ganglion and vagus nerve using gel and reverse-phase high-performance liquid chromatography (HPLC). In each species, a single immunoreactive form of SP co-eluted with the synthetic undecapeptide on a Bio-Gel P-10 column. More than 95% of transported vagal IR-SS co-eluted with synthetic SS-14. A small percentage in each species co-eluted with SS-28. No larger form, corresponding to a prosomatostatin, was identified in any of the 3 species. On HPLC, IR-SP and IR-SS co-eluted with their synthetic forms. To quantify neuropeptide transport, the vagus nerve was ligated distal to the nodose ganglion. 24 h later in each species, the content of IR-SS and IR-SP was more than 6 times greater in a 3-mm segment of nerve proximal to the ligature than in equal length segments distal to ligature or in the unligated contralateral nerve. In the proximal segment, the net content of IR-SP (pg/3-mm segment, mean +/- S.E.M.) was 366 +/- 45 in the rat, 2038 +/- 184 in the guinea pig, and 912 +/- 108 in the cat. The content of IR-SS in the same segment was 36 +/- 4, 66 +/- 13, and 575 +/- 59 pg/3-mm, respectively. The apparent transport velocities were similar for each peptide and among species. The contribution of the nodose ganglion to transported neuropeptide was estimated by crushing the vagus above the nodose ganglion and simultaneously ligating the nerve distal to the ganglion. The percent contribution of the ganglion to transported IR-SS following this procedure was 50% in the rat, 73% in the guinea pig, and 16% in the cat. Nodose ganglion contribution to IR-SP transport was 31%, 50% and 74%, respectively. Estimated turnover of IR-SS and IR-SP within the ganglion ranged from 4.1 to 6.8 times per 24 h in each species.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Axoplasmic transport of somatostatin and substance P in the vagus nerve of the rat, guinea pig and cat. 620 23

Three cases of pancreatic islet cell tumors, 1 malignant and 2 benign, producing predominantly pancreatic polypeptide (PP) are described. All 3 patients exhibited elevated plasma PP concentrations, either basal or protein-meal-stimulated, during the period of observation. Immunocytochemical study revealed that while PP cells predominated in the tumor, A, B, and D cells were also present. A comparison of the hormone content of the tumor tissue, adjacent pancreatic tissue, and normal pancreas was made by radioimmunoassay of tissue extracts. The PP content of tumors clearly exceeded that of normal pancreas. The insulin, glucagon, and somatostatin (SRIF) content was more variable, but in one case the glucagon content of the tumor was higher than in normal pancreas, and two of the tumors exhibited an elevated SRIF content. Gel filtration of a tumor extract showed that insulin, glucagon, and PP immunoreactivity was of expected molecular dimensions but immunoreactive SRIF in this extract was composed of two species. The PP in gel fractions reacted equally well with antibody directed toward different parts of the PP molecule.
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PMID:Pancreatic polypeptide-secreting islet-cell tumors. A study of three cases. 631 15

A porcine kidney microsomal metalloendopeptidase has been enriched 3900-fold. Gel filtration on a calibrated Toyo-Soda G-3000 SW column indicated an appropriate molecular weight for the endopeptidase of 88,000 +/- 2000. The purified enzyme is inhibited by a number of synthetic inhibitors of thermolysin. The endopeptidase hydrolyzes the succinyl (Suc)-containing fluorogenic peptide substrate Suc-Ala-Ala-Phe-(7-amino-4-methylcoumarin) at the Ala-Phe position with a Km of 2.9 X 10(-4) M. The endopeptidase also hydrolyzes a variety of peptides including corticotropin, substance P, angiotensin I and II, neurotensin, somatostatin, bradykinin, and the renin tetradecapeptide substrate. The endopeptidase hydrolyzes both [Leu]- and [Met]enkephalin at the Gly-Phe bond.
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PMID:Purification of a membrane-bound metalloendopeptidase from porcine kidney that degrades peptide hormones. 703 58

The importance of alpha-keto acid binding to plasma proteins was investigated both in vitro and in vivo using alpha-ketoisocaproate (KIC), the alpha-keto acid of leucine. Gel chromatography indicated that 65% of the radioactivity comigrated with serum albumin. An ultrafiltration assay was developed to estimate the percentage of free and bound KIC. These percentages, along with total plasma KIC concentrations, were used to calculate the circulating concentrations of free and bound KIC. KIC or free fatty acids (FFA) displaced [14C]KIC bound to bovine albumin or whole plasma. KIC was totally displaced from plasma proteins by 10 mM oleate, stearate, and myristate; whereas the alpha-keto acids of isoleucine and value were 50 and 85%, respectively, as effective as KIC. To determine whether increased plasma FFA concentrations alter the binding of KIC to plasma proteins in vivo, five postabsorptive humans were infused with triglyceride and heparin during the simultaneous administration of somatostatin, glucagon, and insulin. During the FFA elevation, plasma leucine decreased by 9% (P less than 0.02). Total plasma KIC remained constant, whereas free KIC increased (P less than 0.02) and bound KIC decreased (P less than 0.001). These results indicate that KIC is bound to plasma albumin in vivo and suggests that FFA, by altering circulating free KIC concentrations, may influence protein metabolism in man.
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PMID:Regulation of alpha-ketoisocaproate binding to albumin in vivo by free fatty acids. 703 54

The neuronal biosynthesis of somatostatin-like immunoreactivity (SLI) was investigated using mechanically dispersed neonatal rat hypothalamic cells kept in culture for up to 6 wk. Immunohistochemically, SLI was specifically localized to a small subpopulation of parvicellular neurons and their cell processes. By radioimmunoassay the cellular SLI content declined steadily during the first 2 wk in culture (nadir value of 60 fmol/dish at day 15) but then increased progressively to reach a maximum value of 381 fmol/dish at day 46. Gel chromatographic analysis showed this immunoreactivity to consist of forms corresponding to tetradecapeptide somatostatin (S-14), somatostatin-28 (S-28), and a 15,000-mol-wt molecule. After incubation of the cells with [3H]phenylalanine, the cellular extracts, purified by adsorption to C18 silica, contained material that bound specifically to an immobilized antisomatostatin antibody. Analysis by gel chromatography and high performance liquid chromatography of the specifically bound label provided evidence for the presence of labeled S-14, S-28, and the 15,000-mol-wt molecule. Pulse-chase experiments (20-min pulse, 20-min chase) demonstrated a transfer of radioactivity from the 15,000-mol-wt form to material corresponding to S-14 as well as to S-28. These studies demonstrate that cultured hypothalamic neurons are capable of synthesizing three somatostatin-like peptides (15,000-mol-wt SLI, S-28, S-14), one of which (15,000-mol-wt SLI) serve as a biosynthetic precursor for both S-28 and S-14. This in vitro system should provide a powerful tool for further investigation of the biosynthesis and regulation of biosynthesis of somatostatin in the hypothalamus.
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PMID:Biosynthesis of immunoreactive somatostatin by hypothalamic neurons in culture. 713 Mar 95

A gastric mucosal somatostatin receptor was isolated from the solubilized epithelial cell membrane by affinity chromatography on a column consisting of covalently coupled [D-Tryp8]SRIF-14 to Affi-Gel 10. The receptor protein displayed a molecular weight of 61kDa and exhibited specific affinity towards 125I-labeled [Tyr11]SRIF-14 with the optimum range of 4-8 micrograms/ml. The binding of somatostatin to its mucosal receptor was inhibited by lipopolysaccharide from H. pylori. The inhibitory effect was proportional to the concentration of lipopolysaccharide up to 50 micrograms/ml and reached a maximum of 94.1% inhibition. The results suggest that H. pylori, through its lipopolysaccharide, is capable of interfering with somatostatin regulatory effect on gastric mucosal G-cell function.
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PMID:Helicobacter pylori lipopolysaccharide inhibition of gastric mucosal somatostatin receptor. 754 46

Eight crossbred wethers (51 +/- 2 kg BW), surgically fitted with abomasal cannulas, were used to determine the extent and time course of cysteamine (CSH)-induced depletion of somatostatin (SRIF) in abomasal tissue and associated changes in plasma metabolites, insulin, and growth hormone (GH). Cysteamine was administered as a single i.v. bolus (50 mg.kg BW-1 x 10 min-1) on d 0. Abomasal biopsies were obtained on d -7, -3, 0, 1, 3, and 10. On d 0, additional biopsies were taken at 2, 4, and 8 h after CSH administration. Jugular blood samples were collected over 8 h at 15-min intervals on d -2, 0, and 1. Cysteamine administration decreased (P < .05) tissue SRIF on d 0 (2, 4, and 8 h), 1, and 3; maximal depletion (42 to 55% of Pre-treatment; Pre-trt) occurred during the initial 24 h, returning to Pre-trt by d 10. Gel chromatography of pooled -7 d abomasal tissue extracts showed five peaks of SRIF immunoreactivity; the predominate peak eluted in the same position as synthetic SRIF-14. Plasma glucose, lactate, and NEFA concentrations increased (P = .001) after CSH administration and reached peak at 2 h after treatment and declined to Pre-trt concentrations by 24 h. Insulin increased (P = .001) to a maximum at h 4 and returned to Pre-trt by 24 h. Mean and baseline GH were higher (P < .07) on day of CSH administration, and pulse amplitude was lower (P < .10) on d 0 and 1. These data show that CSH rapidly reduces SRIF in abomasal tissue in a reversible manner; suggesting that CSH-treated sheep may provide a SRIF-deficient model for studying the physiological role of SRIF in ruminants.
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PMID:Cysteamine-induced depletion of somatostatin in sheep: time course of depletion and changes in plasma metabolites, insulin, and growth hormone. 760 57

Cytochrome P450c17, 17 alpha-hydroxylase/17,20 lyase, is a key enzyme in the steroidogenic pathway leading to the production of corticosteroids and androgens from the adrenal gland and sex steroids from the gonads. Both enzymatic activities of the protein are encoded by a single gene, CYP17, which is expressed in both the human adrenal and gonad but not in the placenta, and in the rodent gonad and placenta but not the rodent adrenal. We isolated and sequenced a full-length rat genomic clone (7,553 bases) containing the entire coding region of the rat P450c17 gene, and all intronic sequences and 1,560 bp of 5'-flanking DNA (EMBL Acc#X69816). To determine which sequences in the rat P450c17 promoter may be responsible for basal and cAMP-stimulated gene transcription, deletion constructs containing between -1,560 and -53 base pairs of 5'-flanking DNA from the rat P450c17 gene were ligated to plasmids expressing the reporter gene luciferase and transfected into two mouse cell lines, adrenal Y-1 cells, and testicular Leydig MA-10 cells. Highest basal and cAMP-stimulated luciferase activity were found in constructions containing 156 bp of 5'-flanking DNA. This construction contains a sequence very similar to the consensus cis element reported to be responsible for cAMP enhancement of the rat somatostatin gene and also overlaps a sequence similar to the consensus element for the orphan steroid receptor SF-1. Gel mobility-shift analysis, using a 30-bp oligonucleotide containing this region incubated with cellular extracts from cultured mouse adrenal Y-1 and mouse Leydig MA-10 cells, revealed all the extracts to contain two proteins that bind to this sequence. Neither DNA-protein complex was further retarded by co-incubation with an anti-CREB antibody, suggesting that cAMP regulation of this gene occurs via a non-CREB protein. Mutation of this oligonucleotide resulted in loss of binding of only one of these proteins, but resulted in loss of both basal and cAMP stimulation of rat P450c17 promoter-regulated gene transcription. Southwestern analysis suggests that one of these proteins is larger than SF-1. This study suggests that a protein that binds to an SF-1 like sequence regulates both basal and cAMP-stimulated rat P450c17 gene expression in rodent cells.
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PMID:Transcriptional regulation of rat cytochrome P450c17 expression in mouse Leydig MA-10 and adrenal Y-1 cells: identification of a single protein that mediates both basal and cAMP-induced activities. 770 52

We have measured cerebrospinal fluid (CSF) neuropeptide Y-like immunoreactivity (NPY-LI) and somatostatin-like immunoreactivity (SLI) in control subjects and in patients with various neurologic disorders. We observed a significant reduction in CSF SLI in control subjects over 60 years of age, compared with the younger controls. CSF SLI was significantly decreased in multiple sclerosis (MS), or Guillain-Barre syndrome, compared with that of age-matched control subjects. A reduced concentration of NPY-LI was found in CSF of patients with MS. We have also examined the molecular heterogeneity of peptide-LI in CSF. Gel chromatography, not high performance liquid chromatography (HPLC), suggested two NPY immunoreactive materials in CSF. Gel chromatography and HPLC revealed three SLI components in CSF: somatostatin 14, somatostatin 28 and a higher molecular weight precursor. Our results suggest that 1) there may be more than one form of NPY in human CSF, and 2) somatostatin neurons might be more susceptible to alteration than NPY neurons in various pathological conditions and aging.
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PMID:Cerebrospinal fluid (CSF) neuropeptide Y- and somatostatin-like immunoreactivities in man. 789 40


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