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)

Interleukin 6 is a pleiotropic cytokine produced in the central nervous system (CNS) that has been involved in both direct neurotrophic activities and in the regulation of the production of acute phase proteins both at peripheral and central levels. In rat cortical type I astrocytes, interleukin 6 release is under the control of cAMP-protein kinase A and calcium-phospholipids-protein kinase C systems. Somatostatin is a neuropeptide, acting as a neurotransmitter, highly concentrated within the CNS, where it has been involved in the modulation of learning and memory processes. The aim of this study was to characterize the effects of somatostatin on the release of interleukin 6 from rat cortical type I astrocytes and the intracellular mechanisms involved in this activity. Our results show that somatostatin, in a concentration-dependent manner, inhibited basal and forskolin-stimulated interleukin 6 release from rat cortical type I astrocytes in culture. The EC50 of the inhibitory action was calculated to be approximately 10 nM. Furthermore, this effect of somatostatin was completely abolished by pretreating cortical astrocytes with pertussis toxin that, uncoupling, by ADP-rybosylating, the inhibitory GTP-binding protein from the receptors, prevents the activation of the intracellular effectors such as the adenylyl cyclase enzyme. To identify the intracellular mechanism mediating the effects of somatostatin on the interleukin 6 release, we evaluated the peptide modulation of basal and stimulated intracellular accumulation of cAMP. In our experimental conditions somatostatin significantly inhibited both basal and forskolin-stimulated cAMP accumulation. Conversely, somatostatin did not affect the increase of interleukin 6 release induced by dibutyryl-cAMP, a nonhydrolizable cAMP analog that, bypassing the effects of somatostatin on adenylyl cyclase activity, directly activated protein kinase A. These observations support the hypothesis that somatostatin inhibitory activity on interleukin 6 release is mediated by its effects on cAMP production. Somatostatin analog SMS 201-995 did not affect interleukin 6 production either in basal or stimulated conditions. Since, SMS 201-995 was reported to bind with high affinity only to somatostatin receptors type 2, 3 and 5, the lack of effect of this compound on interleukin 6 release suggests that the inhibitory action of somatostatin could be mediated by the activation of either type 1 or type 4 somatostatin receptors. In conclusion, our data demonstrate that the release of interleukin 6 from rat cortical type I astrocytes is inhibited by somatostatin through the activation of a somatostatin receptor coupled to the inhibition of adenylyl cyclase via a G-protein sensitive to pertussis toxin.
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PMID:Somatostatin inhibits interleukin 6 release from rat cortical type I astrocytes via the inhibition of adenylyl cyclase. 919 70

Trefoil peptides are a family of small proteins expressed by goblet cells that are secreted onto the apical gastrointestinal mucosal surface, where they are present in high concentrations. These peptides appear to both protect the epithelium and promote healing after injury. However, the factors regulating the expression and secretion of these proteins contributing to mucosal defense have not been characterized. To determine the mechanisms controlling production of trefoil peptides, the human colon cancer-derived model cell line HT-29 was exposed to a variety of potential secretagogues. Expression and secretion of human intestinal trefoil factor (hITF) as well as the intestinal apomucin MUC2 were assessed by Northern and Western blot analysis. Carbachol, an analog of acetylcholine, and the neuroendocrine peptides somatostatin and vasoactive intestinal polypeptide (VIP) stimulated increased expression of hITF mRNA within 5 min. These same factors stimulated parallel secretion of the hITF peptide, with maximal stimulation observed at concentrations ranging from 10(-6) M (carbachol and somatostatin) to 10(-7) M (VIP). Expression and secretion of hITF in response to carbachol, VIP, and somatostatin was independent of production of apomucin. hITF was not regulated by other neuroendocrine transmitters including histamine and substance P. Similarly, hITF expression and secretion was not modulated by peptide growth factors (epidermal growth factor, transforming growth factor-beta, and keratinocyte growth factor), cytokines [interleukin (IL)-1 beta, IL-2, IL-7, and IL-11], or arachidonic acid metabolites (prostaglandin E1/E2 and leukotriene B4). In conclusion, trefoil peptides appear to be integrated into mechanisms of mucosal defense and repair through the enteric neuroendocrine system and independent of the classical mucosal immune cytokine network.
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PMID:Trefoil peptide expression and secretion is regulated by neuropeptides and acetylcholine. 927 13

The interaction between components of the nervous system and multiple target cells in the cutaneous immune system has been receiving increasing attention. It has been observed that certain skin diseases such as psoriasis and atopic dermatitis have a neurogenic component. Neuropeptides released by sensory nerves that innervate the skin and often contact epidermal and dermal cells can directly modulate functions of keratinocytes, Langerhans cells (LC), mast cells, dermal microvascular endothelial cells and infiltrating immune cells. Among these neuropeptides the tachykinins substance P (SP) and neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin (SOM) have been reported to effectively modulate skin and immune cell functions such as cell proliferation, cytokine production or antigen presentation under physiological or pathophysiological conditions. Expression and regulation of their corresponding receptors that are expressed on a variety of skin cells as well as the presence of neuropeptide-specific peptidases such as neutral endopeptidase (NEP) or angiotensin-converting enzyme (ACE) determine the final biological response mediated by these peptides on the target cell or tissue. Likewise, skin cells like keratinocytes or fibroblasts are a source for neurotrophins such as nerve growth factor that are required not only for survival and regeneration of sensory neurons but also to control responsiveness of these neurons to external stimuli. Therefore, neuropeptides, neuropeptide receptors, neuropeptide-degrading enzymes and neurotrophins participate in a complex, interdependent network of mediators that modulate skin inflammation, wound healing and the skin immune system. This review will focus on recent studies demonstrating the role of tachykinins, CGRP, SOM and VIP and their receptors and neuropeptide-degrading enzymes in mediating neurogenic inflammation in the skin.
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PMID:Neuropeptides in the skin: interactions between the neuroendocrine and the skin immune systems. 958 47

Murine schistosomiasis mansoni is a parasitic disease in which flukes living in the portal vein of the host produce ova that deposit in the liver and intestines. In these organs, ova release antigens that induce chronic, focal granulomatous inflammation. IFN-gamma is an inflammatory cytokine important in macrophage activation and B-cell differentiation. A substance P (SP)/somatostatin (SOM) neurokine immunoregulatory circuit controls IFN-gamma production in schistosome granulomas. SP stimulates, while SOM inhibits IFN-gamma release, modulating IFN-gamma-dependent circuitry. SP and SOM function through interaction with authentic SP and SOM receptors located on granuloma T cells. Also, the granulomas produce authentic SP and SOM14, as evidenced by the presence of mRNA and product. The granulomas have no nerves. This, and other data suggest that the inflammatory cells make these neurokines. Granuloma macrophages produce SOM. Macrophages from various sources express SOM mRNA in response to LPS, IFN-gamma, IL-10 or several other inflammatory mediators. Thus, the inflammation of murine schistosomiasis has a complete SP/SOM immunoregulatory circuit, which in turn is subject to immunoregulation.
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PMID:The substance P and somatostatin interferon-gamma immunoregulatory circuit. 962 80

Mice infected with the LP-BM5 murine leukemia virus (MuLV) develop an immune deficiency syndrome together with an encephalopathy characterized by impairments in spatial learning and memory. These cognitive deficits are evident before the appearance of neuron loss and lymphoid cell invasion of the brain. Nonetheless, a prominent gliosis and a variety of neurochemical changes precede the development of cognitive deficits. The neurochemical abnormalities include significant decreases in striatal Met-enkephalin and substance P (but not somatostatin), increases in concentrations of quinolinic acid and platelet-activating factor, and alterations in brain fyn kinase. At this stage of the infection, some of these neurochemical changes can be reversed by glutamate receptor antagonists, cytokine inhibitors, and anti-retroviral agents. In later stages of the infection, however, the infected mice develop irreversible neuronal loss, invasion of hematopoietic cells, and increased viral burden in the CNS. In addition, motor-neuron dysfunction (hindlimb paralysis, weakness, and ataxia) and seizures are sometimes observed during the late stages of infection. Thus, the LP-BM5 MuLV-infected mouse is a useful model for studying the chronology of neurodegenerative changes, ranging from reversible neuron dysfunction to irreversible neuron loss, that are associated with retrovirus-induced immunodeficiency.
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PMID:The encephalopathy associated with murine acquired immunodeficiency syndrome. 962 8

FRom several in vitro and in vivo studies involvement of somatostatin (SMS) in intestinal inflammation emerge. Acute colitis induced in rats is attenuated by the long-acting SMS analogue octreotide. We studied the potential beneficial effect of SMS on non-acute experimental colitis. BALB/c mice received either saline, SMS-14 (36 or 120 microg daily) or octreotide (3 microg daily) subcutaneously delivered by implant osmotic pumps. A non-acute colitis was induced by administration of dextran sodium sulphate (DSS) 10% in drinking water during 7 days. DSS evoked a mild, superficial pancolitis, most characterized by mucosal ulceration and submucosal influx of neutrophils. Neither SMS-14 nor octreotide reduced mucosal inflammatory score or macroscopical disease activity, although reduction of intestinal levels of interleukin-1beta (IL-1beta), IL-6 and IL-10 during DSS was augmented both by SMS and octreotide. A slight increase of neutrophil influx was seen during SMS administration in animals not exposed to DSS. In conclusion, SMS or its long-acting analogue did not reduce intestinal inflammation in non-acute DSS-induced colitis. According to the cytokine profile observed, SMS-14 and octreotide further diminished the reduction of intestinal macrophage and Th2 lymphocyte activity.
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PMID:Somatostatin does not attenuate intestinal injury in dextran sodium sulphate-induced subacute colitis. 970 4

Searching for nervous system candidates that could directly induce T cell cytokine secretion, I tested four neuropeptides (NPs): somatostatin, calcitonin gene-related peptide, neuropeptide Y, and substance P. Comparing neuropeptide-driven versus classical antigen-driven cytokine secretion from T helper cells Th0, Th1, and Th2 autoimmune-related T cell populations, I show that the tested NPs, in the absence of any additional factors, directly induce a marked secretion of cytokines [interleukin 2 (IL-2), interferon-gamma, IL-4, and IL-10) from T cells. Furthermore, NPs drive distinct Th1 and Th2 populations to a "forbidden" cytokine secretion: secretion of Th2 cytokines from a Th1 T cell line and vice versa. Such a phenomenon cannot be induced by classical antigenic stimulation. My study suggests that the nervous system, through NPs interacting with their specific T cell-expressed receptors, can lead to the secretion of both typical and atypical cytokines, to the breakdown of the commitment to a distinct Th phenotype, and a potentially altered function and destiny of T cells in vivo.
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PMID:Neuropeptides, by direct interaction with T cells, induce cytokine secretion and break the commitment to a distinct T helper phenotype. 977 May 22

Substance P (SP) and somatostatin (SOM) are made at mucosal surfaces and sites of inflammation. There is a SP/SOM immunoregulatory circuit that modulates the IFN-gamma response in murine schistosomiasis. SP enhances, while SOM decreases, IFN-gamma secretion. Various inflammatory mediators induce macrophages to make SOM, but no known factor limits this expression. It was discovered that SP regulates SOM synthesis. Splenocytes from normal, uninfected mice cultured with LPS, IFN-gamma, or IL-10 for 4 h strongly expressed SOM mRNA, but failed to do so in the presence of SP. The inhibition with 10(-9) M SP was > 85% shown by quantitative PCR. Also, splenocyte SOM content decreased from 1048 +/- 275 to < 10 pg/4 x 10(8) cells following SP exposure. Immunohistochemistry identified SOM solely within splenic macrophages following cytokine stimulation. Mice infected with Schistosoma mansoni form granulomas in the liver and intestines resulting from deposition of parasite eggs in these organs. The granulomas contain macrophages that make SOM constitutively. SP at 10(-8) M decreased SOM mRNA expression > 90% in dispersed granuloma cells cultured for 4 h or longer. Specific SP receptor antagonists blocked SP suppression of SOM expression in splenocytes and dispersed granuloma cells, showing that an authentic SP receptor mediated the regulation. Additional studies revealed that IL-4 antagonized the SP effect in the spleen. It is concluded that in granulomas and splenocytes from mice with schistosomiasis and in splenocytes from uninfected animals that 1) SP inhibits macrophage SOM induction and ongoing expression at the mRNA and protein levels acting through the SP receptor, and 2) IL-4 can antagonizes this SP effect.
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PMID:Substance P regulates somatostatin expression in inflammation. 983 21

Involvement of neuro-endocrineimmune interactions in the development of pathologic responses has been suggested in patients with rheumatoid arthritis (RA). Recently we studied the production of an inhibitory neuropeptide-somatostatin (SOM)--and somatostatin receptor (SOMR) expression in RA synovium and its function in patients with RA. We found that physiologic concentrations of SOM inhibited the proliferation of RA synovial cells. Proinflammatory cytokine and matrix metalloproteinase (MMP) production by RA synovial cells were also inhibited by SOM. Subtype 1 and subtype 2 SOMR were expressed on fibroblast-like synovial cells, and the expression of subtype 2 SOMR was up-regulated with the proinflammatory cytokine treatment of the synovial cells in RA patients. RA fibroblast-like cells synthesized SOM by themselves, suggesting that SOM may act as an autocrine regulator of synovial cell functions in RA patients. SOM and SOM analogues have also been reported to be effective in the treatment of patients with RA. In summary, SOM inhibited aberrant synovial cell functions in patients with RA, suggesting a possible clinical application of this neuropeptide.
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PMID:The role of somatostatin in the pathophysiology of rheumatoid arthritis. 984 73

Tham et al. show that Helicobacter pylori infection lowers the density of immunoreactive somatostatin cells (D-cells) in the antral mucosa and elevates plasma gastrin concentrations. According to current hypothesis, the lack of inhibition by somatostatin allows excessive release of gastrin, which stimulates acid secretion and thus causes duodenal ulcers. The cytokine tumour necrosis factor-alpha which is released in H. pylori gastritis inhibits D-cells in culture and may be responsible. Why do not all infected persons get duodenal ulcers? Recent work shows that more aggressive strains of H. pylori have greater effects on somatostatin/gastrin physiology. Another variable is whether the infection causes corpusitis or not. Inflammation of the gastric corpus diminishes acid secretion, which greatly decreases the likelihood of duodenal ulcers but increases the risk of gastric cancer. Factors which promote corpusitis include diets with high salt content or lacking in antioxidant vitamins. Work in this area is elucidating how H. pylori causes different diseases. Hopefully this will allow us to predict and prevent its serious sequelae.
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PMID:Helicobacter pylori and somatostatin cells. 985 43


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