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)

We have investigated the nature of the immunoreactive somatostatin (SS) and thyrotropin-releasing hormone (TRH) produced by long-term capillary perfusion cultures of rat fetal cortical and hypothalamic cells. Dispersed cortical and hypothalamic cells from 17-day-old fetal rats were injected on to the outer surfaces of separate capillary membrane perfusion systems. Recirculating nutrient medium (Minimum Essential Medium with added glucose, antibiotics and 10% fetal calf serum) was then perfused via the capillary lumen at a rate of 1.5 ml/min and was changed three times weekly. Medium reservoirs, gaseous exchange coils and capillary columns were maintained in a 95% air/5% CO2 environment with 100% humidity. After 6 and 12 days in continuous perfusion, both cortical and hypothalamic cells demonstrated immuno-reactive SS release following 60 mMK+ depolarization (5- to 7-fold increase from basal secretion levels of 15-20 pg/3 X 10(7) cells/10 min). This response was clearly calcium dependent since it was abolished during washes with Ca2+-free Krebs-Ringer bicarbonate solution. Affinity purified material from pooled neuronal perfusates showed three distinct peaks of somatotropin release-inhibiting factor (SRIF) immunoreactivity following polyacrylamide gel chromatography on Biogel-P10. The dominant form coeluted with synthetic tetradecapeptide-somatostatin (SS-14) and a smaller amount (c 30%) coeluted with synthetic SS-28. (The SS-14 antibody used showed equimolar cross reactivity with SS-28). A larger form of immunoreactive material was also detected with an apparent molecular weight of about 11,500 daltons. Hypothalamic and cortical perfusates produced similar electrophoretic patterns of immunoreactive SS (ISS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterisation of somatostatin and TRH release by rat hypothalamic and cerebral cortical neurons maintained on a capillary membrane perfusion system. 613 23

Recent studies have demonstrated that somatostatin-containing cells are in close anatomic proximity to gastrin-producing cells in antral mucosa, suggesting a potential local regulatory role for somatostatin. The purpose of this study was to examine further the relationships between gastrin and somatostatin and the effects of the cholinergic agonist carbachol on content and release of gastrin and somatostatin using rat antral mucosa in tissue culture. Antral mucosa was cultured at 37 degrees C in Krebs-Henseleit buffer, pH 7.4, gassed with 95% O2-5% CO2. After 1 h, the culture medium was decanted and the tissue was boiled to extract mucosal gastrin and somatostatin. Inclusion of carbachol 2.5 X 10(-6) M in the culture medium decreased medium somatostatin from 1.91 +/- 0.28 (SEM) ng/mg tissue protein to 0.62 +/- 0.12 ng/mg (p less than 0.01), extracted mucosal somatostatin from 2.60 +/- 0.30 to 1.52 +/- 0.16 ng/mg (p less than 0.001), and percentage of somatostatin released from 42% +/- 2.6% to 27% +/- 2.2% (p less than 0.01). Carbachol also increased culture media gastrin from 14 +/- 2.5 to 27 +/- 3.0 ng/mg protein (p less than 0.01). Tissue content and release of gastrin and somatostatin were also examined during culture of rat antral mucosa in culture media containing antibodies to somatostatin in the presence and in the absence of carbachol. Incubation with somatostatin antisera, both with and without carbachol, markedly increased culture media concentrations of somatostatin, all of which was effectively bound by antibodies present in the media. Antibody binding of somatostatin was accompanied by significant increases in culture media gastrin concentrations, both in the presence and in the absence of carbachol. Results of these studies support the hypothesis that antral somatostatin exerts a local regulatory effect on gastrin release and that cholinergic stimulation of gastrin release is mediated, at least in part, through inhibition of somatostatin synthesis and release.
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PMID:Effects of carbachol on gastrin and somatostatin release in rat antral tissue culture. 614 13

A superfusion method consisting of fully recovered, dissociated pituitary cells adhering to Cytodex beads has proved useful in monitoring the dynamics of hormone secretion over time. Male rat anterior pituitaries were dissociated with collagenase and Viokase, then cultured in the presence of Cytodex beads for 3-5 days, during which time the cells attached firmly to the surface of the beads. The bead-attached cells were stable and could be transferred to any vessel without the need for centrifugation or further trypsinization. For this application, the bead-attached cells were packed in a column and superfused with a low bicarbonate buffer requiring no CO2 gassing. Viability was more than 95% after 48 h in the column. The cells responded in a normal physiological manner to hypothalamic releasing and inhibitory peptides. The ED50 was 0.3 nM for somatostatin and 1.2 nM for gonadotropin-releasing hormone. A postinhibitory rebound of GH secretion was observed after the discontinuation of large doses of somatostatin. LH secretion reached maximal levels within 6 min after 10 nM gonadotropin-releasing hormone, but started declining after 2 h of continuous stimulation and dropped close to baseline within 18 h. GH release was significantly increased by prostaglandin E2, 3-isobutyl-1-methylxanthine, and 8-bromo-cAMP. LH secretion increased 5-fold in response to 1 mM 8-bromo-cAMP, but showed little increase during prostaglandin E2 or 3-isobutyl-1-methylxanthine stimulation. The cocarcinogen phorbol myristate acetate (12-O-tetradecanoyl-phorbol-13-acetate) induced secretion of all pituitary hormones and continued to do so for hours after a short pulse. The superfusion system is simple to operate and has proven effective in studying transient phenomena, desensitization, and short term kinetics of secretagogues.
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PMID:Superfusion of rat anterior pituitary cells attached to Cytodex beads: validation of a technique. 615 98

Perinatal rat islets of Langerhans, isolated and cultured in vitro, were examined following long-term allotransplantation across a major histocompatibility barrier in nonimmunosuppressed recipients. Islets were isolated to varying degrees of purity without the use of collagenase digestion. Newborn bovine serum was a component of the incubation medium and the atmosphere during culture was air: 5% CO2. Islets transplanted without rigorous purification were fully rejected by 14 days posttransplantation. However, if islets were maintained in subculture, permitting their subsequent meticulous purification, no evidence of rejection was observed after 45 days at the kidney subcapsular site. Grafts consisted of morphologically intact islets. The three major endocrine cell types of the islet were identified by immunocytochemical localization of insulin, glucagon, and somatostatin. These results demonstrate that perinatal islets can exhibit altered immunogenicity, as evidenced by prolonged allograft survival, when isolated and purified by the nonenzymic in vitro method.
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PMID:Modification of allograft immunogenicity in perinatal islets isolated and purified in vitro. 642 93

Reduced O2 availability, as might occur under some physiological and pathological conditions, stimulates insulin and glucagon release and increases glucose fluxes and muscle carbohydrate metabolism. The aim of this study was to determine the role of reduced PO2, independent of changes in glucagon and insulin. In six dogs, in paired studies separated by 2 wk, glucagon and insulin levels were fixed throughout by infusion of somatostatin with basal intraportal glucagon and insulin replacement. A control period was followed by 90 min of breathing 21% (NO) or 8% (LO) O2. Isotopic and arteriovenous methods were used to assess carbohydrate metabolism. Measured variables were constant over time in NO. Arterial PO2 (Pao2) was approximately 100 mmHg in NO and approximately 30 mmHg in LO, resulting in a 50% fall in O2 content. Insulin, glucagon, and catecholamine levels were similar in NO and LO. Cortisol was significantly increased in LO. Arterial glucose was unchanged in both groups. In the last 45 min of the experimental period in LO, 1) glucose production (14 +/- 1 to 18 +/- 1 mumol.kg-1.min-1), glucose disappearance (15 +/- 1 to 17 +/- 1 mumol.kg-1.min-1), and net hepatic glucose output (11 +/- 1 to 15 +/- 1 mumol.kg-1.min-1) rose, 2) limb pyruvate oxidation (11 +/- 2 to 24 +/- 5 mumol/min) and estimated glycogenolysis (9 +/- 3 to 42 +/- 9 mumol/min) increased, 3) percentages of CO2 from limb pyruvate and glucose increased, and percentage of lactate from blood glucose decreased, and 4) arterial blood lactate was approximately 100% more, although net limb and hepatic lactate balances were unaltered, which suggests that neither liver nor muscle is the source of increased blood lactate. Comparison of these results with our previous study [Zinker et al. Am. J. Physiol. 266 (Endocrinol. Metab. 29): E921-E929, 1994] shows that the response to reduced PaO2, although present, is reduced when glucagon and insulin levels are fixed at basal. The majority of stimulation of glucose production by decreased PaO2 is still present when pancreatic hormones are clamped at basal, while the response by the hindlimb tissues is greatly reduced.
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PMID:Contribution of pancreatic hormone responses to the elevation in carbohydrate metabolism with reduced PaO2. 761 94

The effects of somatostatin and atrial natriuretic peptide applied topically to the ventral surface of the medulla (VMS) on tracheal tone and phrenic nerve activity (Phr) were studied in chloralose-anesthetized and paralyzed cats artificially ventilated with 7% CO2 in O2. Surface application of drugs to the chemosensitive areas of the VMS significantly decreased tracheal tension measured by changes in pressure in a balloon placed in a bypassed segment of the trachea (Ptseg). Application of somatostatin (9 cats) caused a mean decrease in Ptseg from 17.3 +/- 1.8 (SE) to 4.3 +/- 1.4 cmH2O (P < 0.01) and a reduction in Phr from 24.9 +/- 3.4 to 10.3 +/- 3.4 units (P < 0.05). Like somatostatin, application of atrial natriuretic peptide to the VMS (5 cats) produced tracheal relaxation (Ptseg decreased from 19.3 +/- 2.6 to 9.9 +/- 1.3 cmH2O, P < 0.01), but in contrast there was an insignificant reduction in Phr (from 18.5 +/- 3.6 to 16.1 +/- 3.8 units, P > 0.05). When parasympathetic activity was abolished by atropine methylnitrate and tracheal tone was restored with 5-hydroxytryptamine, somatostatin and atrial natriuretic peptide applied on the VMS had no effect on tracheal pressure, suggesting that observed changes were not caused by direct action of peptides on tracheal smooth muscle via the bloodstream or by facilitation of inhibitory pathways. Both somatostatin and atrial natriuretic peptide applications were associated with a slight but significant decrease in arterial blood pressure. These data suggest that somatostatin and atrial natriuretic peptide acting on the chemosensitive structure of the VMS may play significant roles in modulating para-sympathetic outflow to airway smooth muscle.
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PMID:Central effects of somatostatin and atrial natriuretic peptide on tracheal tone. 790 23

The anabolic actions of GH are well known, although specific tissue responses and the mechanism of nitrogen conservation are less well understood. This study was designed to examine the acute metabolic effects of GH on whole body and regional protein metabolism, using an experimental protocol which controlled for confounding perturbations in other hormones by a simultaneous infusion of somatostatin. Control subjects received replacement doses of insulin, glucagon, and GH for the entire 7-h study period, whereas GH subjects received an identical protocol, except for an increased dose of GH sufficient to increase serum concentrations into the high-physiological range (12-20 ng/mL) for the final 3.5 h of the study (P < 0.001). Thirteen young, healthy male subjects were studied in the postabsorptive period; five served as control subjects and eight as treatment (GH) subjects. Each received continuous iv infusions of somatostatin, L-[13-C]leucine, and L-[2H5]phenylalanine throughout the study. Femoral arterial and venous sampling allowed for simultaneous measurements across the leg and in the whole body. C-Peptide levels were suppressed throughout the infusion; insulin, glucagon, insulin-like growth factor I, cortisol, epinephrine, norepinephrine, and glucose concentrations were not different between groups. Glycerol concentrations increased 3-fold in GH subjects during the final 3.5-h period (P = 0.04). Concentrations of several amino acids declined through the study, but no differences were observed between treatment groups. Leucine oxidation was reduced in GH compared to control subjects (P = 0.04). No changes in CO2 production or whole body leucine or phenylalanine flux were observed, whereas nonoxidative disposal of leucine was marginally higher in GH compared to control subjects (P = 0.07). By contrast, rates of appearance and disappearance of both leucine and phenylalanine across the leg all were relatively lower in GH compared to control subjects; leucine balance across the leg was reduced by GH (P = 0.03), whereas phenylalanine balance was not influenced by GH. Our data thus demonstrate an acute stimulatory effect of GH on lipolysis, a decrease in leucine oxidation, and no stimulation of muscle protein synthesis in spite of enhanced protein synthesis in nonmuscle tissue.
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PMID:Acute growth hormone effects on amino acid and lipid metabolism. 817 57

Since somatostatin, the growth hormone release-inhibiting hormone, has inhibitory actions in many cell types and is delivered to the anterior pituitary gland via the hypophysial portal vessels, as well as being synthesized by cells within the gland, we tested the hypothesis that it might inhibit the release of gonadotropins from anterior pituitaries in vitro. Consequently, the effect of somatostatin on gonadotropin release from incubated anterior pituitaries of male rats with and without the stimulatory action of luteinizing hormone-releasing hormone (LHRH) was studied. After a preincubation period of 1 hr, hemipituitaries from adult male rats were incubated in fresh Krebs-Ringer bicarbonate (KRB) buffer in a Dubnoff incubator with an atmosphere of 95% O(2)-5% CO2 at 37 degrees C for 3 hr. Incubation with somatostatin (10(-6), 10(-7), and 10(-8) M) had no effect on basal release of either LH or follicle-stimulating hormone (FSH). However, somatostatin (10(-6)-10(-8) M) suppressed LHRH (1.7 x 10(-8) M)-induced release of LH (P < 0.01 to P < 0.0001), but not FSH. Furthermore, somatostatin antiserum (1:1000) had no significant effect on basal LH or FSH release, whereas incubation with the antiserum plus LHRH (1.7 x 10(-9) or 1.7 x 10(-8) M) increased LH (P = 0.015 and P=.005, respectively), but not FSH release. In summary, our results suggest that somatostatin exerts a physiologically significant inhibitory effect on LH but not FSH release in the presence of LHRH in vitro. Presumably, somatostatin is secreted in vitro by pituitary cells since not only have anterior pituitaries of rats been shown to contain somatostatin, but also somatostatin mRNA. Somatostatin then diffuses to the LH gonadotropes, where it exerts its inhibitory action. However, the release of somatostatin is insufficient to alter basal in vitro release. On the other hand, at least at the concentrations employed, there was no significant effect either of somatostatin or the antiserum to alter basal or stimulated FSH release.
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PMID:Effect of somatostatin on the release of gonadotropins in male rats. 901 65

The incretin glucagon-like peptide 1 (GLP-1) shows glucose-dependent insulinotropic activity and may exert anabolic effects. Whole-body protein metabolism was assessed by measuring [1-13C]-leucine kinetics in 13 healthy volunteers during hyperglycaemic clamping with or without pancreatic clamping (somatostatin infusion) in order to differentiate between insulin-mediated and direct GLP-1 effects. During intact pancreatic secretion leucine flux and leucine oxidation rate as parameters of whole-body protein breakdown decreased markedly after 180 min of synthetic GLP-1 infusion (GLP-1 vs. placebo: P < 0.003). Indirect calorimetry showed an increase in energy expenditure and CO2 production during GLP-1 administration (P < 0.0005). Plasma insulin increased after 3h of GLP-1 infusion to 1486 +/- 145 pmol L(-1) vs. 185 +/- 12 pmol L(-1) for saline (P < 0.0001). When plasma insulin levels were kept constant (GLP-1 vs. saline, NS) during pancreatic clamping, GLP-1 effects on both protein metabolism and energy expenditure were abolished. Thus, GLP-1 infusion in man exerts protein anticatabolic and thermic effects, which are mediated by GLP-1-induced stimulation of insulin secretion.
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PMID:Effects of glucagon-like peptide 1 (7-36 amide) on whole-body protein metabolism in healthy man. 904 71

We hypothesized that the direct stimulus of the central chemoreceptor neurons is the CO2/H+-induced change in intracellular pH (pHi). If it is true, pHi responses during hypercapnic stimulation should be exhibited in the central chemoreceptor neurons in the ventral medullary surface (VMS) and some neurons in the CO2/H+ sensitive regions such as the nucleus tractus solitarii of the medial dorsal medulla (MDM). To test this hypothesis, the cultured VMS and MDM neurons (control) derived from one day-old neonate rats were labeled with H+-sensitive fluorescent indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF), and were exposed to perfusate of various pHs. The H+-sensitive neurons were determined by a rapid decrease in the intracellular BCECF fluorescence intensity. In almost all the MDM neurons (99.6%) and 94% of the VMS neurons, the intracellular BCECF fluorescence intensity remained unchanged when the extracellular pH (pHo) was decreased. In contrast, in 0.4% of the MDM neurons (8/1800) and in 6% of the VMS neurons (111/1800), the intracellular BCECF fluorescence intensity decreased when the pHo was decreased from 7.4 to 7.2. This subpopulation of MDM and VMS neurons were considered to be H+-sensitive neurons. The H+-sensitive neurons in the VMS showed positive immunoreactivity to glutamate (57%, 17/30) and glutamic acid decarboxylase (23%, 7/30), but no immunoreactivity to choline acetyltransferase, tyrosine hydroxylase, phenylethanolamine N-methyltransferase, somatostatin, serotonin and substance P. These results indicate that the H+-sensitive neurons are present specifically in the VMS, and are mainly glutamatergic and GABAergic.
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PMID:In vitro study of H+-sensitive neurons in the ventral medullary surface of neonate rats. 944 17


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