Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of organic and inorganic nitrovasodilators (sodium nitroprusside; 3-morpholinosydnonimine; glyceryl trinitrate; isosorbide dinitrate; sodium nitrite, was studied on the release of histamine evoked by compound 48/80 and calcium ionophore A 23187 in isolated purified rat serosal mast cells. All the compounds tested were capable of significantly reducing the release of histamine in a concentration-dependent fashion, at different levels of potency. This effect was reverted by oxyhaemoglobin. The inhibitory effect of glyceryl trinitrate on the release of histamine was potentiated in cells taken from animals pretreated with Escherichia coli lipopolysaccharide, and decreased by NG-nitro-L-arginine methyl ester. Glyceryl trinitrate and isosorbide dinitrate concentration-dependently increase the generation of nitric oxide by rat serosal mast cells. The inhibitory effect of glyceryl trinitrate and isosorbide dinitrate on the release of histamine from mast cells was potentiated by N-acetylcysteine, which significantly increases the generation of nitric oxide by mast cells. It is concluded that nitrovasodilators inhibit the release of mast cell histamine through the generation of nitric oxide. The effect may be relevant in considering the perivascular location of mast cells and the role played by these cells in cardiovascular pathophysiology.
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PMID:Generation of nitric oxide from nitrovasodilators modulates the release of histamine from mast cells. 751 83

This study was initiated to test the hypothesis that histamine can act as an endothelium-derived contracting factor in bovine isolated intrapulmonary vein. The effects of calcium ionophore, calcimycin (A23187), on isometric tension were compared in unstimulated rings of intrapulmonary vein with and without endothelium. A23187 (0.1-10 microM) induced concentration-related contraction when endothelium was present. Destruction of endothelium markedly inhibited A23187-induced contraction. Methylene blue, hemoglobin or NG-methyl-L-arginine significantly enhanced A23187-induced contraction only in venous rings with endothelium consistent with attenuation of the contraction by the concomitant release of endothelium-derived relaxing factor (nitric oxide) [EDRF(NO)]. Histamine H1 receptor antagonists inhibited, and iproniazid enhanced, contraction elicited by A23187. A23187 induced release of greater amounts of histamine from venous rings with than without endothelium. A23187-induced contraction was not mimicked by the mast cell activator, compound 48/80, and was not inhibited by preexposure to compound 48/80 or in the presence of cromolyn or doxantrazole. A23187-induced contraction was not inhibited by pretreatment with indomethacin, phentolamine, lipoxygenase inhibitors or superoxide dismutase. The results indicate that A23187 induces endothelium-dependent contraction in bovine intrapulmonary vein and support histamine as one major mediator involved. The association of destruction of endothelium with an inhibition of both A23187-induced contraction and histamine release is consistent with the endothelium as a source for histamine which can exert a local vasoconstrictor effect in bovine intrapulmonary vein.
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PMID:Evidence that histamine is involved as a mediator of endothelium-dependent contraction induced by A23187 in bovine intrapulmonary vein. 752 73

The results of the current study demonstrate that relaxin inhibits histamine release by mast cells. This effect is related to the peptide concentrations, and could be observed in both isolated rat serosal mast cells stimulated with compound 48/80 or calcium ionophore A 23187, and in serosal mast cells isolated from sensitized guinea pigs and challenged with the antigen. The morphological findings agree with the functional data, revealing that relaxin attenuates calcium ionophore-induced granule exocytosis by isolated rat serosal mast cells. Similar effects of relaxin have also been recognized in vivo by light microscopic and densitometric analysis of the mesenteric mast cells of rats which received the hormone intraperitoneally 20 min before local treatment of the mesentery with calcium ionophore. Moreover, evidence is provided that relaxin stimulates endogenous production of nitric oxide and attenuates the rise of intracellular Ca2+ concentration induced by calcium ionophore. The experiments with drugs capable of influencing nitric oxide production also provide indirect evidence that the inhibiting effect of relaxin on mast cell histamine release is related to an increased generation of nitric oxide. It is suggested that relaxin may have a physiological role in modulating mast cell function through the L-arginine-nitric oxide pathway.
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PMID:Effects of relaxin on mast cells. In vitro and in vivo studies in rats and guinea pigs. 752 51

Nitric oxide (NO)-synthase immunoreactivity has been detected for the first time in mast cells of human normal nasal mucosa, with an antibody specific for neuronal NO-synthase. Intense immunoreactivity was revealed in secretion granules of mast cells but was found in mast cell granules free in the extracellular matrix only in some instances; no reactivity was found in the cytoplasm of this or other cell types. These findings suggest that human nasal mast cells contain a particulate isoform of NO-synthase, which shares epitopes with neuronal NO-synthase and is rapidly removed from granules upon exocytosis.
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PMID:Localization of nitric oxide synthase immunoreactivity in mast cells of human nasal mucosa. 752 57

The aim of the present study was to investigate whether or not release of endogenous mast cell mediators modulates exocytotic noradrenaline overflow. Therefore, we perfused rat isolated hearts with the right sympathetic innervation intact and investigated the effect of mast cell degranulation on the efflux of noradrenaline. Compound 48/80 (48/80), a mast cell degranulating agent, caused a large release of histamine and serotonin and a facilitation of evoked noradrenaline overflow. When 48/80 was introduced into the perfusion medium 4 min before sympathetic nerve stimulation (SNS), evoked noradrenaline overflow was increased by about 60%. In the presence of the uptake 1-blocker cocaine, facilitation was attenuated (increase by only 30%). This effect was abolished by the histamine H2 receptor antagonist cimetidine or the inhibitor of nitric oxide synthesis NG-nitro-(L)-(-)-arginine. When the preexposure time to 48/80 was reduced to 30 s, the facilitation was less pronounced (15%) and inverted to an inhibition in the presence of cocaine (plus idazoxan) by 17% and/or cimetidine (by about 30%). The resulting inhibition of noradrenaline efflux was attenuated by the serotonin 5-HT1/2 receptor antagonist methiothepin or the 5-HT2 antagonist ketanserin. Infusion of ovalbumin into hearts of not specifically sensitized, but sham treated rats (in vivo injection of a saline-alumina mixture 10-12 days before the in vitro experiment) did not affect histamine, serotonin or (basal and evoked) noradrenaline efflux. In hearts from rats that were previously sensitized by an injection of an ovalbumin-alumina adsorbate, ovalbumin induced a marked increase of histamine and serotonin efflux. When the infusion of the antigen started 30 s before SNS, evoked noradrenaline overflow was inhibited by about 60%. The inhibition was unaffected by histamine receptor antagonists, but attenuated by purinoceptor (suramin plus 1,3-dipropyl-8-cyclopentylxanthine), or serotonin receptor (methiothepin, rauwolscine or ketanserin) antagonists. When the preexposure time to ovalbumin was prolonged to 4 min before SNS, no significant change of stimulation-induced noradrenaline overflow was observed. Basal, immunologically and non-immunologically induced histamine and serotonin efflux were not significantly affected by SNS or any of the drugs tested. The results indicate a complex influence of various mediators released upon mast cell degranulation induced by two different stimuli on exocytotic noradrenaline release from rat heart. Depending on the stimulus and on the time interval between the start of the application of the mast cell degranulating agent and SNS, a histamine- and nitric oxide-mediated facilitation, or a serotonin- and purine-mediated inhibition prevails.
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PMID:Differential effects on sympathetic neurotransmission of mast cell degranulation by compound 48/80 or antigen in the rat isolated perfused heart. 753 Jul 91

Terminal nerve fibres of the autonomic nervous system closely approach mast cells in peripheral organs, and mutual influences between release of neurotransmitters or mast cell mediators may cause neuro-immunological interactions. We have studied the influence of mast cell degranulation on the release of endogenous noradrenaline and newly incorporated acetylcholine (such as 14C-choline/acetylcholine overflow) evoked by stimulation of extrinsic postganglionic sympathetic or preganglionic vagal nerves in the rat Langendorff heart perfused with Tyrode solution. Compound 48/80 perfused in normal hearts, or ovalbumin infused into hearts from rats sensitized to ovalbumin, enhanced the overflow of endogenous histamine and serotonin. Both stimuli increased the release of mediators to a similar extent and with fast kinetics. Maximum average concentrations in the perfusate of histamine were about 800 nmol/l, and of serotonin 40 nmol/l, in a sample collected within 4 min after mast cell degranulation. Stimulation of autonomic nerves did not affect basal histamine or serotonin overflow. Whereas basal overflows were unaffected, the stimulation-evoked releases of both noradrenaline and acetylcholine, were facilitated when compound 48/80 was perfused before and during nerve stimulation. The facilitation of noradrenaline overflow was more pronounced (by 60%) when compound 48/80-induced mediator overflow started 4 min before nerve stimulation as compared to 30 s (15%), and was reduced by cocaine (by 50%), and, in the presence of cocaine, abolished by cimetidine (but was unaffected by mepyramine and thioperamide) and NG-nitro-(L)-(-)-arginine. In the presence of cimetidine and cocaine, when the facilitatory components were abolished, the evoked noradrenaline overflow observed 30 s after the start of infusion of compound 48/80 was inhibited, and the inhibition was partly reduced by methiotepin and ketanserin. Ovalbumin infusion in hearts from sensitized animals caused an inhibition of evoked noradrenaline overflow sensitive to methiotepin and also partly to ketanserin, and no facilitation was observed. The facilitation (> 100%) of evoked overflow of acetylcholine observed at 4 min after the start of perfusion with compound 48/80 was partly reduced by thioperamide (but not mepyramine or cimetidine) and to a comparable extent either by tropisetron (3 mumol/l) alone or by tropisetron plus methiotepin. In conclusion, degranulation of immunological cells is followed by histamine and serotonin release in the rat heart and may affect the release of autonomic neurotransmitters in rather unusual ways, by i) an uptake1-dependent and ii) an H2-mediated facilitation which probably involves nitric oxide as a permissive mediator, and iii) a serotonergic inhibition, of noradrenaline release, and iv) an H3- and serotonergic facilitation of acetylcholine release.
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PMID:Histamine and serotonin released from the rat perfused heart by compound 48/80 or by allergen challenge influence noradrenaline or acetylcholine exocytotic release. 753 2

The objective of this study was to determine whether an inhibitor of nitric oxide (NO) synthase (NG,NG'-dimethyl-L-arginine; L-DMA) that is produced by vascular endothelium elicits the inflammatory responses induced by synthetic analogues of L-arginine such as NG-nitro-L-arginine methyl ester (L-NAME). Leukocyte adherence and emigration, leukocyte-platelet aggregation, and albumin leakage were monitored in rat mesenteric venules exposed to different concentrations of either L-DMA or L-NAME. Increases in leukocyte adherence (7- to 9-fold) and emigration (3- to 5-fold), platelet-leukocyte aggregation, mast cell degranulation, and an enhanced albumin leakage (30-50%) were observed within 30 min after exposing the microvascular bed to either inhibitor; however, leukocyte emigration and albumin leakage responded more intensely to L-NAME than to L-DMA. The microvascular alterations and mast cell degranulation were attenuated by addition of L-arginine to the superfusate. These results suggest that the L-DMA is capable of eliciting an inflammatory response at concentrations detected in plasma under certain pathological conditions.
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PMID:Effects of an endogenous inhibitor of nitric oxide synthesis on postcapillary venules. 754 59

Nitric oxide (NO.) plays a central role in the physiology of the gastrointestinal tract and its response to critical illness. Potential sources of NO. in the gut include: intrinsic intestinal tissue (mast cells, epithelium, smooth muscle, neural plexus), resident and/or infiltrating leukocytes (neutrophils, monocytes), reduction of luminal gastric nitrate, and denitrification by commensal anaerobes. The brain and endothelial isoforms of nitric oxide synthase are expressed under resting conditions, whereas inflammatory stimuli are required for the induction of the inducible type. Under resting conditions, mucosal perfusion is regulated by NO. derived from the vascular endothelium of the mesenteric bed. During inflammation, excessive NO. production from the inducible synthase may contribute to mucosal hyperemia. Coordination of peristalsis and sphincteric action is mediated by the release of NO., which acts as the principal neurotransmitter of the nonadrenergic, noncholinergic enteric nervous system. Alterations in bowel motility, such as ileus, result from excessive concentrations of NO. generated during endotoxicosis and inflammatory bowel disease. The role of NO. in the regulation of salt and water secretion is poorly understood. Endotoxin-induced inhibition of gastric acid secretion appears to be mediated by the action of NO. on parietal cells. NO. may protect the gastrointestinal mucosa from a variety of stimuli (caustic ingestion, ischemia, ischemia/reperfusion injury, early endotoxic shock) by maintaining mucosal perfusion, inhibiting neutrophil adhesion to mesenteric endothelium, blocking platelet adhesion, and preventing mast cell activation. Excessive NO., however, may directly injure the mucosa. Barrier function of the intestinal mucosa is protected by NO. in the early stages of injury, when neutrophil adhesion, ischemia, and mast cell activation are relevant. Inhibition of NO. synthesis ameliorates barrier dysfunction during more advanced stages of inflammation, when activation of inducible NOS yields toxic concentrations of NO.. At high concentrations, NO. disrupts the actin cytoskeleton, inhibits ATP formation, dilates cellular tight junctions, and produces a hyperpermeable state. Selective inhibition of the inducible isoform of NOS and maintenance of the constitutive types may be therapeutic.
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PMID:Nitric oxide in the gut. 758 76

Nitric oxide (NO.) plays a central role in the Physioliology of the gastrointestinal tract and its response to critical illness. Potential sources of NO. in the gut include: intrinsic intestinal tissue (mast cells, epithelium, smooth muscle, neural plexus), resident and/or infiltrating leukocytes (neutrophils, monocytes), reduction of luminal gastric nitrate, and denitrification by commensal anaerobes. The brain and endothelial isoforms of nitric oxide synthase are expressed under resting conditions, whereas inflammatory stimuli are required for the induction of the inducible type. Under resting conditions, mucosal perfusion is regulated by NO. derived from the vascular endothelium of the mesenteric bed. During inflammation, excessive NO. production from the inducible synthase may contribute to mucosal hyperemia. Coordination of peristalsis and sphincteric action is mediated by the release of NO., which acts as the principal neurotransmitter of the nonadrenergic, noncholinergic enteric nervous system. Alterations in bowel motility, such as ileus, result from excessive concentrations of NO. generated during endotoxicosis and inflammatory bowel disease. The role of NO. in the regulation of salt and water secretion is poorly understood. Endotoxin-induced inhibition of gastric acid secretion appears to be mediated by the action of NO. on parietal cells. NO. may protect the gastrointestinal mucosa from a variety of stimuli (caustic ingestion, ischemia, ischemia/reperfusion injury, early endotoxic shock) by maintaining mucosal perfusion, inhibiting neutrophil adhesion to mesenteric endothelium, blocking platelet adhesion, and preventing mast cell activation. Excessive NO., however, may directly injure the mucosa. Barrier function of the intestinal mucosa is protected by NO. in the early stages of injury, when neutrophil adhesion, ischemia, and mast cell activation are relevant. Inhibition of NO. synthesis ameliorates barrier dysfunction during more advanced stages of inflammation, when activation of inducible NOS yields toxic concentrations of NO.. At high concentrations, NO. disrupts the actin cytoskeleton, inhibits ATP formation, dilates cellular tight junctions, and produces a hyperpermeable state. Selective inhibition of the inducible isoform of NOS and maintenance of the constitutive types may be therapeutic.
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PMID:Nitric oxide in the gut. 770 93

There is growing evidence that nitric oxide (NO.), a biologically active gas continuously produced by endothelium, is a homeostatic regulator of leukocyte adhesion in the microcirculation. Inhibition of NO. production leads to increased leukocyte rolling and adhesion in various vascular beds and two adhesion molecules, P-selectin and CD11/CD18, have been implicated in these processes. The role of mast cells and mast cell-derived mediators as potential contributors to the increased adhesion are discussed in this review. Moreover, oxidants may initiate the leukocyte recruitment after NO. synthesis inhibition. Recent data demonstrating increased oxidative stress in endothelium deprived of NO. are summarized. The role of NO. as an anti-inflammatory and antiadhesive modulator in postischemic venules of various organs is also discussed. The beneficial effect of NO. donors in this inflammatory condition is summarized. Finally, the potential use of NO. donating drugs in concert with available pharmaceutical compounds to reduce inflammation is reviewed.
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PMID:Nitric oxide is an antiadhesive molecule for leukocytes. 770 96


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