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)

Using 1-ethyl-3(3-dimethyl-aminopropyl)-carbodiimide (EDAC) fixation and immunocytochemical confocal microscopic study, bright serotonin and histamine fluorescence appeared in the nucleus of rat peritoneal mast cells. In case of paraformaldehyde fixation, this was not observed. The phenomenon can be explained by the cross-linking effect of EDAC, which did not allow the efflux of biogenic amines from the nucleus. This means that biogenic amines are present in the nucleus of mast cells, and this is supported by the flow cytometric measurement data of the whole cell. Other hormones studied (triiodothyronine, insulin, and endorphin) were not present in the nucleus. Four pharmaca with biogenic amine-influencing character in the central nervous system were used for studying the relation between the external (surrounding and cytoplasmic) and nuclear biogenic amine content of mast cells. Fluoxetine, a serotonin reuptake inhibitor depleted nuclear as well as cytoplasmic serotonin content. Clorgyline, a MAO-A inhibitor, decreased cytoplasmic serotonin content and weakened nuclear serotonin fluorescence. The tryptophan hydroxylase inhibitor, para-chlorophenylalanine (PCPA), and the mast cell degranulator, Compound 48/80, reduced cytoplasmic serotonin content without influencing nuclear content. Histamine fluorescence was influenced solely by fluoxetine. The results show that nuclear 5-HT content is dependent firstly of serotonin uptake and reuptake. To our knowledge, this is the first exact report on the presence of non-steroid-type-receptor-transported hormones inside the nucleus of a cell.
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PMID:Hormones in the nucleus. Immunologically demonstrable biogenic amines (serotonin, histamine) in the nucleus of rat peritoneal mast cells. 1633 78

Testectomy increased serotonin content in fluorescent granular macrophages of the subcapsular and premedullary zones and in mast cell granules. Serotonin concentrations in the medullary and cortical thymocytes decrease. Young sudanophilic mast cells with low content of proteoglycans and low-sulfated immature heparin predominate in the gland after testectomy.
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PMID:Reaction of thymic monoamine-containing structures to experimental testectomy. 1675 25

5-Hydroxytryptamine (5-HT) activates colonic splanchnic afferents, a mechanism by which it has been implicated in generating symptoms in postinfectious and postinflammatory states in humans. Here we compared mechanisms of colonic afferent activation by 5-HT and mechanical stimuli in normal and inflamed rat colon, and after recovery from inflammation. Colonic inflammation was induced in rats by dextran sulphate sodium. Single-fibre recordings of colonic lumbar splanchnic afferents revealed that 58% of endings responded to 5-HT (10(-4) m) in controls, 88% in acute inflammation (P<0.05) and 75% after 21 days recovery (P < 0.05 versus control). Maximal responses to 5-HT were also larger, and the estimated EC50 was reduced from 3.2 x 10(-6) to 8 x 10(-7) m in acute inflammation and recovered to 2 x 10(-6) m after recovery. Responsiveness to mechanical stimulation was unaffected. 5-HT3 receptor antagonism with alosetron reduced responses to 5-HT in controls but not during inflammation. Responses to the mast cell degranulator 48/80 mimicked those to 5-HT in inflamed tissue but not in controls, and more 5-HT-containing mast cells were seen close to calcitonin gene-related peptide-containing fibres in inflamed serosa. We conclude that colonic serosal and mesenteric endings exhibit increased sensitivity to 5-HT in inflammation, with both an increase in proportion of responders and an increase in sensitivity, which is maintained after healing of inflammation. This is associated with alterations in the roles of 5-HT3 receptors and mast cells.
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PMID:Increased responsiveness of rat colonic splanchnic afferents to 5-HT after inflammation and recovery. 1713 6

Myrtaceae is a plant family widely used in folk medicine and Syzygium and Eugenia are among the most important genera. We investigated the anti-allergic properties of an aqueous leaf extract of Syzygium cumini (L.) Skeels (SC). HPLC analysis revealed that hydrolyzable tannins and flavonoids are the major components of the extract. Oral administration of SC (25-100 mg/kg) in Swiss mice (20-25 g; N = 7/group) inhibited paw edema induced by compound 48/80 (50% inhibition, 100 mg/kg; P <or= 0.05) and, to a lesser extent, the allergic paw edema (23% inhibition, 100 mg/kg; P <or= 0.05). SC treatment also inhibited the edema induced by histamine (58% inhibition; P <or= 0.05) and 5-HT (52% inhibition; P <or= 0.05) but had no effect on platelet-aggregating factor-induced paw edema. SC prevented mast cell degranulation and the consequent histamine release in Wistar rat (180-200 g; N = 7/group) peritoneal mast cells (50% inhibition, 1 microg/mL; P <or= 0.05) induced by compound 48/80. Pre-treatment of BALB/c mice (18-20 g; N = 7/group) with 100 mg/kg of the extract significantly inhibited eosinophil accumulation in allergic pleurisy (from 7.662 +/- 1.524 to 1.89 +/- 0.336 x 10(6)/cavity; P <= 0.001). This effect was related to the inhibition of IL-5 (from 70.9 +/- 25.2 to 12.05 +/- 7.165 pg/mL) and CCL11/eotaxin levels (from 60.4 +/- 8.54 to 32.8 +/- 8.4 ng/mL) in pleural lavage fluid, using ELISA. These findings demonstrate an anti-allergic effect of SC, and indicate that its anti-edematogenic effect is due to the inhibition of mast cell degranulation and of histamine and serotonin effects, whereas the inhibition of eosinophil accumulation in the allergic pleurisy model is probably due to an impairment of CCL11/eotaxin and IL-5 production.
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PMID:Pharmacological study of anti-allergic activity of Syzygium cumini (L.) Skeels. 1722 3

Intracranial headaches such as migraine are thought to result from activation of sensory trigeminal pain neurons that supply intracranial blood vessels and the meninges, also known as meningeal nociceptors. Although the mechanism underlying the triggering of such activation is not completely understood, our previous work indicates that the local activation of the inflammatory dural mast cells can provoke a persistent sensitization of meningeal nociceptors. Given the potential importance of mast cells to the pain of migraine it is important to understand which mast cell-derived mediators interact with meningeal nociceptors to promote their activation and sensitization. In the present study, we have used in vivo electrophysiological single-unit recording of meningeal nociceptors in the trigeminal ganglion of anesthetized rats to examine the effect of a number of mast cell mediators on the activity level and mechanosensitivity of meningeal nociceptors. We have found that that serotonin (5-HT), prostaglandin I(2) (PGI(2)), and to a lesser extent histamine can promote a robust sensitization and activation of meningeal nociceptors, whereas the inflammatory eicosanoids PGD(2) and leukotriene C(4) are largely ineffective. We propose that dural mast cells could promote headache by releasing 5-HT, PGI(2), and histamine.
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PMID:Sensitization and activation of intracranial meningeal nociceptors by mast cell mediators. 1748 91

Herbex-kid (HK), a polyherbal formulation was evaluated in various experimental allergic models of Type I hypersensitivity reactions. Compound 48/80 (C 48/80) has been shown to induce rat mesentery mast cell degranulation and HK (1.07, 10.75 and 107.5 mg ml(-1)) inhibited the mast cell degranulation in a dose dependent manner. HK (1.07, 10.75 and 107.5 mg kg(-1); p.o.) showed dose-dependent protection against C 48/80 induced systemic anaphylaxis in male Balb/C mice. In active anaphylaxis model, male Wistar rats orally administered with 10.75 and 107.5 mg kg(-1) of HK showed significant (P < 0.01) protection against mast cell degranulation, while in passive anaphylaxis model, only at 107.5 mg kg(-1) showed significant (P < 0.01) reduction in mast cell degranulation. HK at all dose levels was able to significantly decrease the time spent in nasal rubbing in Wistar rats sensitized to ovalbumin, while only at 107.5 mg kg(-1) it showed significant (P < 0.01) reduction in number of sneezes. In C 48/80-induced skin itch model, all dose levels of HK significantly (P < 0.001) decreased the time spent in itching and the number of itches. HK did not produce any significant inhibition in histamine induced contraction in guinea pig ileum. From the above findings we conclude that the HK possesses antiallergic activity mediated by reducing of the release mediators from mast cells and also by 5-HT antagonism without the involvement of histamine (H1) receptors.
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PMID:Herbex-kid Inhibits Immediate Hypersensitivity Reactions in Mice and Rats. 1883 Apr 58

The present study was designed to examine the effects of a sesquiterpene lactone isolated from Artemisia douglasiana Besser (dehydroleucodine), a xanthanolide sesquiterpene isolated from Xanthium cavanillesii Schouw (xanthatin) and a semisynthetic butenolide (3-benzyloxymethyl-5H-furan-2-one) on mast cell degranulation induced by compound 48/80. Peritoneal mast cells from male adult Sprague-Dawley rats were purified in Percoll, preincubated in the presence of test lactones (dehydroleucodine, xanthatin or 3-benzyloxymethyl-5H-furan-2-one) and then challenged with the mast cell activator compound 48/80 (10 microg/ml). Concentration-response and kinetic studies of mast cell serotonin release evoked by compound 48/80, evaluation of mast cell viability and morphology by light and electron microscopy, and comparative studies using ketotifen and sodium chromoglycate were carried out. Serotonin release studies, carried out together with morphological studies, showed the effectiveness of the above lactones to stabilize mast cells. The comparative study with ketotifen and sodium chromoglycate, well known mast cell stabilizers, showed the following order of potency dehydroleucodine=xanthatin>3-benzyloxymethyl-5H-furan-2-one> or =ketotifen/sodium chromoglycate to inhibit mast cell serotonin release induced by compound 48/80. The present study provides the first strong evidence in favour of the hypothesis that dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit compound 48/80-induced serotonin release from peritoneal mast cells, acting thus as mast cell stabilizers. Our findings may provide an insight into the design of novel pharmacological agents which may be used to regulate the mast cell response.
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PMID:Novel anti-ulcer alpha,beta-unsaturated lactones inhibit compound 48/80-induced mast cell degranulation. 1934 8

Rat airways exposure to Staphylococcal enterotoxin A (SEA) and B (SEB) induces marked neutrophil influx. Since sensory neuropeptides play important roles in cell infiltration, in this study we have investigated its contribution in triggering SEA- and SEB-induced pulmonary neutrophil infiltration. Male Wistar rats were exposed intratracheally with SEA (3 ng/trachea) or SEB (250 ng/trachea). Animals received different in vivo pretreatments, after which the neutrophil counts and levels of substance P and IL-1 in bronchoalveolar lavage fluid were evaluated. Alveolar macrophages and peritoneal mast cells were incubated with SEA and SEB to determine the IL-1 and TNF-alpha levels. Capsaicin pretreatment significantly reduced SEA- and SEB-induced neutrophil influx in bronchoalveolar lavage fluid, but this treatment was more effective to reduce SEA responses. Treatments with SR140333 (tachykinin NK(1) receptor antagonist) and SR48968 (tachykinin NK(2) receptor antagonist) decreased SEA-induced neutrophil influx, whereas SEB-induced responses were inhibited by SR140333 only. Cyproheptadine (histamine/5-hydroxytriptamine receptor antagonist) and MD 7222 (5-HT(3) receptor antagonist) reduced SEA- and SEB-induced neutrophil influx. The substance P and IL-1 levels in bronchoalveolar lavage fluid of SEA-exposed rats were significantly higher than SEB. In addition, SEA (but not SEB) significantly released mast cell TNF-alpha. Increased production of TNF-alpha and IL-1 in alveolar macrophages was observed in response to SEA and SEB. In conclusion, sensory neuropeptides contribute significantly to SEA- and SEB-induced pulmonary neutrophil recruitment, but SEA requires in a higher extent the airways sensory innervation, and participation of mast cells and alveolar macrophage products.
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PMID:Role of sensory innervation in the rat pulmonary neutrophil recruitment induced by staphylococcal enterotoxins type A and B. 1937 18

We addressed the mechanism by which antigen contracts trachea isolated from actively sensitized mice. Trachea were isolated from mice (C57BL/6J) that had been actively sensitized to ovalbumin (OVA). OVA (10 microg ml(-1)) caused histamine release (approximately total tissue content), and smooth muscle contraction that was rapid in onset and short-lived (t(1/2) < 1 min), reaching approximately 25% of the maximum tissue response. OVA contraction was mimicked by 5-HT, and responses to both OVA and 5-HT were sensitive to 10 microm-ketanserin (5-HT(2) receptor antagonist) and strongly inhibited by atropine (1microm). Epithelial denudation had no effect on the OVA-induced contraction. Histological assessment revealed about five mast cells/tracheal section the vast majority of which contained 5-HT. There were virtually no mast cells in the mast cell-deficient (sash -/-) mouse trachea. OVA failed to elicit histamine release or contractile responses in trachea isolated from sensitized mast cell-deficient (sash -/-) mice. Intracellular recordings of the membrane potential of parasympathetic neurons in mouse tracheal ganglia revealed a ketanserin-sensitive 5-HT-induced depolarization and similar depolarization in response to OVA challenge. These data support the hypothesis that antigen-induced contraction of mouse trachea is epithelium-independent, and requires mast cell-derived 5-HT to activate 5-HT(2) receptors on parasympathetic cholinergic neurons. This leads to acetylcholine release from nerve terminals, and airway smooth muscle contraction.
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PMID:Mast cell-cholinergic nerve interaction in mouse airways. 1940 9

Mast cells of a number of different animal species have been reported to contain serotonin (5-hydroxytryptamine; 5-HT), a monoamine capable of numerous and complex actions, which may include an impact on tumour growth. Limited previous studies have suggested that normal or neoplastic canine mast cells do not express 5-HT. In the present study, canine cutaneous mast cell tumours (MCTs) of Patnaik histological grades I-III were investigated immunohistochemically for expression of 5-HT and its receptor (R) 5-HT1A. The proportion of positively labelled cells and the intensity of labelling of individual cells were determined. Both 5-HT and the 5-HT1A receptor were expressed by non-neoplastic dermal mast cells and neoplastic mast cells. More neoplastic mast cells expressed 5-HT than the 5-HT1AR. Poorly differentiated tumours expressed fewer of both molecules, but the better differentiated mast cells at the periphery of such lesions had more consistent 5-HT expression. 5-HT and the 5-HT1A receptor may be involved in the differentiation of canine MCTs and in the microvascular complications associated with these neoplasms.
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PMID:Expression of serotonin and its 5-HT1A receptor in canine cutaneous mast cell tumours. 1944 35


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