Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Unlike human mast cells associated with mucosal surfaces such as lung, adenoids, tonsils and intestine, skin mast cells may be stimulated to release histamine by the neuropeptides substance P, vaso-active intestinal polypeptide and somatostatin or by other basic secretagogues such as morphine and compound 48/80. Release of histamine by neuropeptides is rapid and accompanied by minimal generation of the eicosanoids prostaglandin D2 and leukotriene C4. Transient elevations of intracellular calcium are associated with mediator secretion induced by both immunological and non-immunological stimulation, that induced by anti-IgE being derived from extracellular sources through channels in the plasma membrane while that stimulated by neuropeptides is mobilized intracellularly. Similarly, elevations of intracellular cyclic AMP induced by anti-IgE occur only in the presence of extracellular calcium, whereas with substance P elevations are apparent even in the absence of extracellular calcium. With the latter stimulus, histamine release is complete before the peak cyclic AMP is achieved. Despite these biochemical and temporal differences, degranulation induced by both secretagogues proceeds by compound exocytosis which is indistinguishable under the electron microscope. From these results we suggest that IgE-dependent and neuropeptide stimulation of human skin mast cells proceed by distinct biochemical pathways which eventually merge to produce exocytosis of their preformed granule-associated mediators.
 ...
PMID:Neuropeptide-induced secretion from human skin mast cells. 171 93

In AtT-20 cells somatostatin inhibits the secretion of adrenocorticotropic hormone (ACTH) through the activation of GTP binding proteins (G proteins) linked to second messengers such as calcium and cyclic AMP (cAMP). Recently, it has been proposed that there may be G proteins that regulate directly the exocytotic machinery. We have investigated whether somatostatin could inhibit secretion at a step distal to second messengers through a GTP binding protein. For these studies two experimental paradigms were used: (1) intact cells stimulated by calcium ionophores and (2) digitonin-permeabilized cells exposed to buffers of increasing Ca2+ concentrations. Somatostatin inhibited by 70% the ACTH release caused by the calcium ionophore ionomycin without modifying the ionophore-induced elevation in cytosolic [Ca2+]. This effect was cAMP independent because (1) it was observed in the presence of high concentrations of membrane-permeant cAMP analogues, and (2) it was not accompanied by a change in cAMP levels. The effect was also independent of the levels of activators of protein kinase C because it could be produced in the presence of high concentrations of phorbol esters. The action of somatostatin was prevented by pertussis toxin. In digitonin-permeabilized AtT-20 cells somatostatin inhibited release induced by calcium buffers in a GTP-dependent manner. These two observations indicate the involvement of a G protein. It is proposed that a G protein coupled to somatostatin receptors inhibits the intracellular machinery of secretion at a step distal to second messengers, perhaps at the exocytotic site.
 ...
PMID:Evidence that receptor-linked G protein inhibits exocytosis by a post-second-messenger mechanism in AtT-20 cells. 196 44

Some beta-adrenergic receptor (beta AR) antagonists, in addition to blocking receptor-mediated responses, possess agonistic properties or intrinsic sympathomimetic activity (ISA). In this study we describe several techniques for amplification of cAMP levels as a measure of agonistic activity, and we apply these techniques to the study of beta AR antagonists with ISA. We show that 1) a variety of beta AR antagonists with ISA, including alprenolol and cyanopindolol, enhance cyclic AMP accumulation in S49 lymphoma cells if cells are also incubated with the diterpene forskolin; 2) beta AR blockers with ISA stimulate cAMP accumulation in the presence of a water-soluble analog of forskolin but not in the presence of 9,11-dideoxyforskolin (which does not activate adenylyl cyclase); 3) the potentiation by forskolin is not unique to S49 cells but is also observed in BC3H1 smooth muscle-derived cells; 4) stimulation of cAMP accumulation by beta-blockers with ISA occurs in S49 cells in three additional settings that do not involve the use of forskolin, after pretreatment with pertussis toxin to inactivate the inhibitory guanine nucleotide binding protein, after pretreatment with [D-Trp8]-somatostatin to sensitize adenylyl cyclase, and using a radioimmunoassay to quantitate levels of cellular cAMP. We conclude that beta AR antagonists with ISA can weakly stimulate intracellular cAMP accumulation, but this stimulation is not easily detected. Elevation of cAMP levels may account for the agonistic effects of these drugs or, at least provides a measure of stimulatory guanine nucleotide-binding protein activation by these compounds.
 ...
PMID:Amplification of cyclic AMP generation reveals agonistic effects of certain beta-adrenergic antagonists. 196 18

The effects of endogenous hypothalamic neurohormones and activators of second messenger signalling systems on the secretion of GH and on cell content of GH mRNA of cultured bovine adenohypophysial cells were studied. Synthetic bovine GH-releasing factor (bGRF; 100 nmol/l) increased secretion of GH by bovine adenohypophysial cells five-fold relative to control. Forskolin (an adenyl cyclase activator; 10 mumol/l) and the synthetic cyclic AMP analogue dibutyryl cyclic AMP (dbcAMP; 1 mmol/l) increased secretion of GH by 1.9- and 1.7-fold respectively, relative to control. The protein kinase C activator phorbol 12-myristate 13-acetate (PMA), provided at 1 mumol/l or 10 nmol/l, increased GH secretion by 6.6- and four-fold respectively, relative to control. Somatostatin-14 (SRIF-14) attenuated basal, bGRF-, forskolin- and dbcAMP-stimulated secretion of GH by 40, 49, 47 and 67% respectively, but did not, however, diminish PMA-stimulated GH secretion. The content of GH mRNA in cultured bovine adenohypophysial cells increased 2.2-, 1.7- and 3.2-fold by administration of bGRF, forskolin and PMA respectively, relative to control. Although GH mRNA content was unchanged by SRIF-14 treatment relative to control, SRIF-14 did reduce bGRF-stimulated bGH mRNA content by 67%. This study demonstrates that mechanisms subserving GH secretion in bovine adenohypophysial cells (e.g. adenyl cyclase and protein kinase C) may be coupled with mechanisms which regulate expression of the GH gene or with factors affecting message stability.
 ...
PMID:Modulation of growth hormone (GH) secretion and GH mRNA levels by GH-releasing factor, somatostatin and secretagogues in cultured bovine adenohypophysial cells. 197 Oct 2

The interaction of adrenergic and peptide receptors linked to adenylate cyclase and the inhibition by bioactive peptides of stimulated cyclic AMP production has been investigated in intact, excised rabbit ciliary processes. Cyclic AMP production stimulated by isoproterenol, vasoactive intestinal peptide, or forskolin was inhibited by the biologically active peptides neuropeptide Y, somatostatin, and the synthetic somatostatin analogue SMS 201-995. IC50s determined from dose-response curves of inhibition are consistent with the known abilities of these ligands to modulate cyclic AMP and physiological responses in other tissues. Inhibition by neuropeptide Y or SMS 201-995 was unaffected by the specific alpha 2-adrenergic antagonist yohimbine, which shows that peptide inhibition is not occurring via peptide binding to the inhibitory alpha 2-adrenergic receptor. These results suggest that endogenous peptides may participate in modulation of cyclic AMP production and subsequent physiological events influenced by cyclic AMP levels in rabbit ciliary processes by inhibiting stimulated cyclic AMP synthesis.
 ...
PMID:Neuropeptide Y and somatostatin inhibit stimulated cyclic AMP production in rabbit ciliary processes. 197 Dec 7

The mechanisms involved in inhibition of insulin secretion by somatostatin and noradrenaline were compared in order to establish whether the receptors for these agents are coupled to similar effector systems in the pancreatic B cell. Both agents significantly reduced forskolin-induced adenylate cyclase activity in islet homogenates, although noradrenaline was more effective than somatostatin. The capacity of noradrenaline to inhibit insulin secretion was largely unaffected by agents that increase intracellular cyclic AMP, whereas the effect of somatostatin as an inhibitor was markedly reduced under these conditions. Both noradrenaline and somatostatin inhibited the stimulation of insulin secretion induced by K+ depolarization, but different mechanism were involved. Somatostatin significantly inhibited K(+)-stimulated 45Ca2+ efflux and influx in islets, while noradrenaline exerted only a minor influence on these processes. The data indicate that noradrenaline controls insulin secretion by a mechanism which operates beyond the level of intracellular messenger generation. In contrast, somatostatin exerts at least part of its inhibitory effect on insulin secretion by directly controlling islet cell Ca2+ influx in a manner which may be regulated by cyclic AMP.
 ...
PMID:Evidence for differential effects of noradrenaline and somatostatin on intracellular messenger systems in rat islets of Langerhans. 197 36

The cyclic AMP (cAMP) response element-binding protein (CREB) has been demonstrated to be a key mediator of cellular promoter response to cAMP. The binding site for this protein in many cellular cAMP inducible promoters (CRE) contains the palindrome sequence TGACGTCA, which contains two half-sites for CREB binding. A related promoter element, with the core sequence TGACG, has significant homology to an AP1-binding site and contains only one half-site for CREB binding. A group of factors known as activating transcription factors (ATF) have been found to bind to the latter and related sequences found upstream of early adenovirus promoters induced by E1A, and these factors are highly homologous to the CREB protein. We wished to characterize CREB, c-jun, and c-fos binding to these sites in the somatostatin gene (CRE) and in the adenovirus early region 3 promoter (E3/ATF). Oligonucleotides complementary to each of these sites were used in gel retardation assays with in vitro-translated CREB protein. These studies indicated that CREB bound primarily as a dimer to both a single and two half-sites, though there was increased affinity to the double compared with the single half-site. The c-jun and c-fos proteins also bound to both the somatostatin CRE- and E3/ATF-binding sites, but CREB did not bind to AP1 recognition sites nor was it capable of forming heterodimers with either c-jun or c-fos. Truncations of the CREB protein, which eliminated regions of the protein containing consensus sites for phosphorylation by protein kinase A, protein kinase C, and casein kinase II, bound to both the CRE and ATF sites, indicating that these consensus sites were not essential for DNA binding or dimer formation. Transfection of CREB and protein kinase A expression constructs into F9 cells with promoters containing either a single or two half-sites for CREB binding indicated that CREB was capable of similar levels of activation of these constructs. However, the fold activation by CREB was higher for constructs containing a single half-site compared with those containing two half-sites. These results demonstrate that multiple mechanisms may regulate CREB binding, including variations in the sequences in the promoter-binding site and the presence of related DNA-binding proteins.
 ...
PMID:CREB regulation of cellular cyclic AMP-responsive and adenovirus early promoters. 197 51

Freshly dissociated cerebral cortex cells from adult rats have been used in the present study to determine if dual regulation of cyclic AMP levels by inhibitory and stimulatory agents can be expressed in the mature brain. Somatostatin, an inhibitory agent, barely affected the basal cyclic AMP metabolism while vasoactive intestinal peptide (VIP) and isoproterenol, two stimulatory agents enhanced cyclic AMP production. However, this increase was depressed by somatostatin, which decreased the efficiency, but not the potency, of the effects of the two stimulatory agents on cyclic AMP accumulation.
 ...
PMID:Somatostatin inhibition of VIP- and isoproterenol-stimulated cyclic AMP accumulation in dissociated cells from rat cerebral cortex. 197 62

Somatostatin was incubated in an adenylate cyclase assay of a particulate fraction of caudate-putamen tissue of the rat in order to examine the effect of the peptide on D-1 receptor coupled adenylate cyclase in vitro. Somatostatin was able to enhance cyclic AMP formation in the presence of guanylylimidodiphosphate and guanosine-triphosphate. In contrast to this, somatostatin inhibited both dopamine and forskolin-stimulated cyclic AMP accumulation. Pertussis toxin and cholera toxin also depressed forskolin-induced stimulation. Somatostatin was found to antagonize these inhibitory effects of pertussis toxin and cholera toxin. The results suggest that somatostatin acts through a stimulatory as well as an inhibitory guanine nucleotide regulatory protein subtype to affect dopaminergic adenylate cyclase activity.
 ...
PMID:Somatostatin acts through G-proteins on dopaminergic adenylate cyclase in the caudate-putamen of the rat. 198 58

We have examined the binding of factors in rat liver nuclear extracts to the phosphoenolpyruvate carboxykinase (PEPCK) gene cyclic AMP (cAMP) response element (CRE) and other CREs and have isolated a rat liver CRE-binding protein (CREBP) cDNA. In addition, we have examined the influence of altering the phosphorylation state of nuclear factors on both CRE binding and in vitro transcription. Specific binding to the PEPCK CRE was measured in a mobility shift assay. CRE sequences of the PEPCK, somatostatin, and glycoprotein hormone alpha subunit genes competed equally for binding of rat liver nuclear factors to the PEPCK CRE, whereas mutant PEPCK CRE sequences did not compete for binding. Oligonucleotides complementary to rat pheochromocytoma CREBP (Gonzalez et al., Nature [London] 337:749-752, 1989) were used to prime rat liver and brain cDNA in the polymerase chain reaction. The predominant CREBP molecule obtained was identical to the rat pheochromocytoma CREBP except for a 14-amino-acid deletion in the N-terminal half that was also present in a human placental cDNA (Hoeffler et al., Science 242:1430-1433, 1988). The regulation of transcription by cAMP was examined by coincubation of rat liver nuclear extract with the purified catalytic subunit of cAMP-dependent protein kinase (protein kinase A). Although binding to the CRE was unaffected, in vitro transcription directed by the PEPCK promoter was stimulated by catalytic subunit, and this effect was blocked by protein kinase inhibitor peptide. In contrast, when nuclear extract was coincubated with phosphatase, there was substantial inhibition of in vitro transcription directed by the PEPCK promoter, but there was no effect on binding to the CRE. The major effects of catalytic subunit were exerted through the CRE, but residual stimulation was evident in promoter fragments containing only the TATA element. These data suggest that factors are bound to the CRE at constitutively high levels and that their capacity for transcriptional activation is regulated by phosphorylation.
 ...
PMID:Cyclic AMP-dependent protein kinase regulates transcription of the phosphoenolpyruvate carboxykinase gene but not binding of nuclear factors to the cyclic AMP regulatory element. 214 84


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>