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)

Intracerebroventricular (ICV) injection of interleukin (IL)-1 alpha has previously been demonstrated to enhance the rate of whole body glucose disposal. The purpose of the present study was to identify the specific tissue(s) responsible for the increased glucose uptake. All experiments were performed on fasted catheterized rats in which an ICV cannula had also been implanted. In vivo glucose uptake by individual tissues was determined, using tracer amounts of [14C]-2-deoxyglucose, 20-60 min after the ICV injection of recombinant human IL-1 alpha (100 ng/rat). IL-1 increased glucose uptake in skeletal muscle (117%), diaphragm (50%) and heart (110%), compared to time-matched control animals. Glucose uptake by other tissues, including the liver, spleen, lung, skin, ileum and whole brain, was not different from control values. As a result of these changes, the contribution of skeletal muscle to whole body glucose disposal increased from 29% to 48%, while that of skin and intestine decreased. The increased glucose uptake in various muscles was consistent with the increased (55%) plasma insulin levels in these animals. In rats pretreated with somatostatin, which produced severe insulinopenia, the IL-1 induced increases in glucose uptake were prevented in heart and diaphragm, and attenuated by more than 80% in skeletal muscle. These data indicate that the increased whole body glucose disposal produced by ICV injection of IL-1 alpha was due to an enhanced uptake of glucose by muscle via insulin-mediated pathways.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Central administration of IL-1 alpha increases glucose uptake by muscle. 774 67

Using the passive avoidance learning task in rats, the role of brain somatostatin in cognitive function was investigated with special reference to that of the brain cholinergic system. In addition, the involvement of both the brain somatostatinergic and cholinergic systems in the anti-amnesic action of a newly introduced cognitive enhancer, FR121196 [N-(4-acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide], was examined. Treatment with cysteamine (50, 100, 200 mg/kg, s.c.), a depletor of somatostatin, significantly and dose-dependently reduced the retention of single trial passive avoidance task. Similar memory impairments were found in rats which received central cholinergic blockade either by scopolamine (0.1-1 mg/kg) or by lesioning of the nucleus basalis magnocellularis (NBM). Intracerebroventricurally (i.c.v.) administered somatostatin (1-14) (10-1000 ng/rat) significantly ameliorated the memory impairments induced not only by cysteamine (200 mg/kg) but also by scopolamine (1 mg/kg) and NBM-lesioning. Although physostigmine (0.01-1 mg/kg) also ameliorated the memory impairments induced by cysteamine and scopolamine, it failed to affect the memory impairment seen in the NBM-lesioned rats. Administration of FR121196 (0.1-10 mg/kg) significantly ameliorated the memory deficits produced by scopolamine and NBM lesioning but not that induced by cysteamine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Possible involvement of brain somatostatin in the memory formation of rats and the cognitive enhancing action of FR121196 in passive avoidance task. 791 90

Suppressed pulsatile GH secretion in food-deprived rats has been hypothesized to be due to an increase in hypothalamic somatostatin secretion. We investigated this hypothesis and the role of GHRH in regulating GH secretion during food deprivation using two different models. In experiment one, rats were food deprived for 72h during which time they received a saline infusion (n = 5). At the same time rats were normal fed for 72h during which time they received a somatostatin infusion (5 micrograms/h, n = 7). After the 72h infusion period, all rats received two iv injections of GHRH (1 microgram/rat) at 2h intervals. GH concentrations in food-deprived rats rose from approximately 10 ng/ml to 400-800 ng/ml in response to both GHRH injections. This increase was significantly greater (p < 0.01) than the GH response (100-400 ng/ml) observed in somatostatin-infused animals. The significantly higher GH response observed in food-deprived rats as compared to somatostatin-infused, normal-fed rats suggests that somatostatin concentrations may decrease during food deprivation. In experiment two, rats were infused for 5h with either saline (n = 6) or GHRH (10 micrograms/h, n = 9) at the end of a 72h fast. GH concentrations did not change in saline-infused animals. In contrast, GH concentrations significantly increased (p < 0.01) upon initiation of the continuous GHRH infusion. Yet, this release of GH was pulsatile in nature. Pulsatile GH secretion in the presence of a constant GHRH infusion suggests that pulsatile somatostatin release from the hypothalamus is maintained during food deprivation. These studies suggest that during food deprivation in the rat 1) absolute concentrations of somatostatin decrease, but its pattern of secretion remains pulsatile, and 2) decreased GHRH release may be responsible for the absence of spontaneous GH pulses.
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PMID:Hypothalamic regulation of growth hormone secretion during food deprivation in the rat. 809 16

The effect of octreotide, a synthetic analogue of somatostatin, on the modulation of the acetic acid model of experimental colitis was examined. Colitis was induced by intracolonic administration of 2 ml of 5% acetic acid. The inflammatory response elicited by the acetic acid resulted in increased colonic synthesis of platelet activating factor, leukotriene B4 and decreased mucosal somatostatin levels. Subcutaneous administration of octreotide (10 micrograms/rat) 1 hour before or immediately after damage induction, as well as 1 and 23 hours after acetic acid application, resulted in a significant reduction in mucosal damage. The protective effect was accompanied by a significant reduction in platelet activating factor activity, leukotriene B4, and vasoactive intestinal peptide concentrations. There were no significant changes in mucosal leukotriene C4 and calcitonin gene related peptide levels. This study shows that acetic acid induced colitis is pharmacologically manipulated by octreotide. The mechanism of action of octreotide has not yet been fully determined. The potential use of octreotide in treating active inflammatory bowel disease remains to be evaluated.
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PMID:Octreotide effectively decreases mucosal damage in experimental colitis. 838 60

The mechanisms involved in 2-deoxy-D-glucose (2-DG)-induced growth hormone (GH) suppression in the rat were examined. Conscious male rats were given 2-DG by intracerebroventricular (icv) injection and the pulsatile GH secretion was monitored for 6 h. The single icv injection of 2-DG (8 mg/rat) eliminated pulsatile GH secretion in conscious rats. Pretreatment with somatostatin (SS) antiserum completely restored the suppressed GH secretion in the 2-DG treated rats. Hypothalamic GH-releasing hormone (GRH) and SS mRNA levels were not altered by single and multiple icv injections of 2-DG. These findings suggest that 2-DG-induced GH suppression is primarily due to hypersecretion of SS without a significant change at the transcription level in the rat.
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PMID:Central glucopenia induced by 2-deoxy-D-glucose stimulates somatostatin secretion in the rat. 856 23

We investigated whether somatostain modulates the generation of long-term potentiation (LTP) in rat perforant path-dentate gyrus synapse in vivo. When somatostatin was injected intracerebroventricularly (i.c.v.) 20 min prior to the tetanus, the intensity of LTP increased dose dependently. Synaptic potential evoked by a low-frequency test stimulation, however, was not altered by somatostatin. We next tested whether the LTP-augmenting effect of somatostain is mediated by cholinergic activation, because somatostatin was demonstrated to promote acetylcholine release in rat hippocampal slice. Pirenzepine (50 nmol/rat), a muscarinic M1 receptor antagonist, did not affect the tetanus-induced LTP by itself. But when it was co-applicated with the somatostatin (50 ng/rat) 20 min before tetanus, it completely abolished the LTP-augmenting effect of somatostatin. Then we examined the effect of octreotide, a potent agonist specifically binding to somatostatin receptor subtypes 2 and 4, on the generation of LTP. Octreotide (500 ng/rat) also facilitated the intensity of LTP. These results suggest that somatostatin facilitates the generation of perforant path-dentate gyrus granule cell LTP by activating the muscarinic cholinergic receptor and the effect of somatostatin is induced, at least partly, by somatostatin receptor subtypes 2 and 4 in vivo.
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PMID:Facilitatory role of somatostatin via muscarinic cholinergic system in the generation of long-term potentiation in the rat dentate gyrus in vivo. 881 90

Somatostatin and its analogs act in the brain to influence gastric acid secretion. Five different somatostatin receptor subtypes have been characterized (sst1 to sst5). We studied the influence of somatostatin (0.18-0.6 nmol/rat) and selective sst2, sst3 and sst5 receptor ligands on basal gastric acid secretion in conscious rats equipped with chronic gastric and intracerebroventricular (i.c.v.) cannulae. Somatostatin-14 (0.36 nmol/rat), the sst2, sst3 and sst5 receptor agonist, Des-AA1,2,4,5,12,13-[D-Tryp8,D-Cys14]somatostatin (SMS 201-995) (0.18-0.36 nmol/rat) and the sst5 receptor agonist, BIM-23052, (0.8-1.2 nmol/rat) injected i.c.v. inhibited gastric acid secretion. Maximal inhibition reaching 42%, 60% and 42% was induced by somatostatin-14 (0.36 nmol/rat), SMS 201-995 (0.18 nmol/rat) and BIM-23052 (0.8 nmol/rat) respectively. The sst2 receptor agonist, DC 32-87 (0.2-0.8 nmol/rat) and sst3 receptor agonist, BIM-23056 (0.2-1.2 nmol/rat), did not modify gastric acid secretion, except the sst3 receptor agonist at 0.4 nmol/rat which increased acid output at 20 min post-injection. The sst2 receptor agonists (0.4 nmol/rat) co-injected i.c.v. with a subthreshold dose of sst5 (0.4 nmol/rat) inhibited gastric acid secretion. These results show that i.c.v. injection of somatostatin-14 inhibits basal gastric acid secretion in conscious rats through an action on sst5 receptor subtype which can be potentiated by sst2 receptor subtype.
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PMID:Intracerebroventricular injection of somatostatin sst5 receptor agonist inhibits gastric acid secretion in rats. 883 51

Although there is evidence that suggests that dopamine (DA) has stimulatory effects on somatostatinergic transmission, it is unknown to date if DA increases the activity of the somatostatin (SS) receptor-effector system in the rat brain. In this study, we evaluated the effects of the administration of DA and the DA D1-like (D1, D5) receptor antagonist SCH 23390 and the D2-like (D2, D3, D4) receptor antagonist spiperone on the SS receptor-adenylate cyclase (AC) system in the Sprague-Dawley rat striatum and hippocampus. An intracerebroventricular injection of DA (0.5 microgram/rat) increased the number of SS receptors and decreased their apparent affinity in the striatum and hippocampus 15 hr after its administration. The simultaneous administration of the DA receptor antagonists SCH 23390 (0.25 mg/kg, ip) and spiperone (0.1 mg/kg, ip) before DA injection partially prevented the DA-induced increase in SS binding. The administration of SCH 23390 plus spiperone alone produced a significant decrease in the number of SS receptors in both brain areas studied at 15 hr after injection, an effect that disappeared at 24 hr. The increased number of SS receptors in the DA-treated rats was associated with an increased capacity of SS to inhibit basal and forskolin (FK)-stimulated (AC) activity in the striatum and hippocampus at 15 hr after injection. This effect had disappeared at 24 hr. By contrast, basal and FK-stimulated enzyme activities were unaltered after DA injection. No significant changes in the levels of the alpha i (alpha i1 + alpha i2) subunits were found in DA-treated rats as compared with control rats. In addition, the immunodetection of the alpha i1 or alpha i2 subunits showed no significant changes in their levels in DA-treated rats when compared with controls. DA injection also induced an increase in SS-like immunoreactive content in the rat striatum but not hippocampus at 15 hr after administration and returned to control values at 24 hr. These results provide direct evidence of a functional linkage between the dopaminergic and somatostatinergic systems at the molecular level.
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PMID:Dopamine enhances somatostatin receptor-mediated inhibition of adenylate cyclase in rat striatum and hippocampus. 916 Feb 46

To generate antibodies to defined cell-surface antigens, we used a large phage antibody fragment library to select on cell transfectants expressing one of three chosen receptors. First, in vitro panning procedures and phage antibody screening ELISAs were developed using whole live cells stably expressing the antigen of interest. When these methodologies were applied to Chinese hamster ovary (CHO) cells expressing one of the receptors for a neuropeptide, somatostatin, using either direct cell panning or a strategy of depletion or ligand-directed elution, many different pan-CHO-cell binders were selected, but none was receptor specific. However, when using direct panning on CHO-cells expressing the human membrane protein CD36, an extraordinary high frequency of antigen-specific phage antibodies was found. Panning on myoblasts expressing the rat homologue of CD36 revealed a similar selection dominance for anti-(CD36). Binding of all selected 20 different anti-(CD36) phage was surprisingly inhibited by one anti-(CD36) mAb CLB-IVC7, which recognizes a functional epitope that is also immunodominant in vivo. Similar inhibition was found for seven anti-(rat) CD36 that cross-reacted with human CD36. Our results show that, although cells can be used as antigen carriers to select and screen phage antibodies, the nature of the antigen target has a profound effect on the outcome of the selection.
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PMID:Selection-dominant and nonaccessible epitopes on cell-surface receptors revealed by cell-panning with a large phage antibody library. 1010 7

Radiolabelled tumour receptor-binding peptides can be used for in vivo scintigraphic imaging. Recently, the somatostatin analogue [Tyr3]octreotide (D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr(ol)) was derivatized with the chelator DOTA (tetra-azacyclododecane-tetra-acetic acid), enabling stable radiolabelling with both the high-energy beta particle-emitter yttrium-90 and the Auger electron-emitter indium-111. The thus produced radiolabelled compounds are promising for peptide receptor radionuclide therapy. Our previous in vitro and in vivo (rat) experiments with these radiolabelled compounds showed favourable binding and biodistribution characteristics with high uptake and retention in the target organs. We also demonstrated receptor-specific, time- and temperature-dependent internalization of radiolabelled [DOTA0,Tyr3]octreotide in somatostatin receptor subtype 2 (sst2)-positive rat pancreatic tumour cell lines. In this study we have investigated the effects of differences in the amount of injected peptide on tissue distribution of 111In-labelled [DOTA0, Tyr3]octreotide in normal, i.e. non-tumour-bearing, and CA20948 tumour-bearing rats. This was done in order to find the amount of peptide at which the highest uptake in target tissues is achieved, and thereby to increase the potential of radionuclide therapy while simultaneously ensuring the lowest possible radiotoxicity in normal organs. Uptake of radiolabelled [DOTA0,Tyr3]octreotide in sst2-positive organs showed different bell-shaped functions of the amount of injected peptide, being highest at 0.05 (adrenals), 0.05-0. 1 (pituitary and stomach) and 0.25 (pancreas) microg. Uptake in the tumour was highest at 0.5 microg injected peptide. The highest uptake was found at peptide amounts that were lower than those reported for [111In-DTPA0]octreotide ((D-Phe-c(Cys-Phe-D-Trp-Lys-Thr-Cys)-Thr(ol), DTPA = diethylene-triamine-penta-acetic acid), consistent with the higher receptor affinity of the first compound. Our observations of mass-dependent differences in uptake of radiolabelled [DOTA0, Tyr3]octreotide, being the resultant of a positive effect of increasing amounts of peptide on, for example, receptor clustering and a negative effect of receptor saturation, are of consequence for rat radionuclide therapy studies with radiolabelled peptides and may also be of consequence for human radionuclide therapy studies with this compound.
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PMID:Tumour uptake of the radiolabelled somatostatin analogue [DOTA0, TYR3]octreotide is dependent on the peptide amount. 1039 16


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