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

Histamine release from dispersed skin mast cells may be used for functional studies on the mast cell. However, technical difficulties have hampered such studies. In the present study a new fiberglass-based histamine assay was applied to previously described dispersion techniques, using excision biopsies from 7 patients with urticaria pigmentosa, 3 with psoriasis as well as 4 with urticaria. However, sufficient mast cell numbers for performing histamine release could only be obtained from patients with urticaria pigmentosa. The average mast cell yield was 935 +/- 470 cells (mean +/- SD) per mg wet weight of tissue. The skin mast cells from these patients responded with dose-dependent histamine release to anti-IgE, calcium ionophore A23187, and N-formyl-methionyl-leucyl-phenylalanine challenge without previous passive sensitization. The pattern of histamine release of mast cells and corresponding blood basophils did not indicate substantial differences between the two cell types.
 ...
PMID:Histamine release from skin mast cells and basophils in patients with urticaria pigmentosa. 169 Apr 93

Previously, we demonstrated that through binding a novel intracellular receptor of microM affinity (HIC), histamine mediates, and the HIC antagonist N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine. HCl (DPPE) inhibits, platelet aggregation and serotonin granule secretion; the latter response is dependent upon the same processes that mediate histamine release from mast cell granules. We now show that, as for platelet serotonin release, DPPE blocks concanavalin A-stimulated mast cell histamine release with a potency (IC50 = 30 microM) greater than the H1-antagonist, pyrilamine (IC50 = 150 microM) or the H2-antagonist cimetidine (IC50 = 5 mM), correlating with rank order of potency to inhibit 3H-histamine binding in rat brain membranes and liver microsomes. We postulate that histamine release from mast cells is mediated at HIC by second messenger intracellular histamine. However, unlike platelets, mast cells do not appear to rely on newly synthesized histamine. Rather, as for calcium, histamine may be mobilized from bound stores to mediate histamine secretion.
 ...
PMID:Does intracellular histamine mediate mast cell histamine release? 169 Sep 90

A mouse spleen-derived mast cell line (PT-18) was employed to examine the mechanisms of adenosine 3':5'-monophosphate (cAMP)-mediated inhibition of antigen-induced lipid mediator biosynthesis. Specifically, we tested the hypothesis that increasing cAMP in mast cells inhibits lipid mediator biosynthesis by a mechanism independent of effects on histamine release (degranulation) or changes in cytosolic calcium concentration. Forskolin inhibited antigen-induced prostaglandin D2 (PGD2), leukotriene C4 (LTC4), and leukotriene B4 (LTB4) production by 30-50%. In contrast, forskolin had no inhibitory effect on antigen-induced increases in cytosolic calcium concentration, as monitored by the calcium indicator fura-2, or histamine release from the cells. The combination of the phosphodiesterase inhibitor isobutylmethylxanthine with forskolin inhibited the antigen-induced production of PGD2 and LTC4 by 90-100% and histamine release by about 60%. These responses were accompanied by a virtual abolition of the antigen-induced increase in cytosolic calcium. To test further the hypothesis that increasing cAMP can lead to inhibition of lipid mediator biosynthesis in the absence of effects on cytosolic calcium, we employed the calcium ionophores A23187 and ionomycin. Forskolin alone or in combination with isobutylmethylxanthine had no effect on ionophore-induced increases in cytosolic calcium but effectively inhibited leukotriene biosynthesis. In addition, increasing cyclic AMP led to an inhibition of ionophore-induced production of platelet-activating factor and liberation of arachidonic acid. These data suggest that a relatively modest increase in cAMP-dependent protein kinase activity in mast cells leads to inhibition of the lipase-catalyzed cleavage of arachidonic acid from membrane phospholipids in the absence of measurable effects on either histamine release or changes in cytosolic calcium concentration. This effect results in a selective inhibition of the biosynthesis of lipid mediators including LTC4, LTB4, PGD2, and platelet-activating factor.
 ...
PMID:Inhibition by adenosine 3':5'-monophosphate of eicosanoid and platelet-activating factor biosynthesis in the mouse PT-18 mast cell. 169 Nov 75

In this study we investigated the effects of long wave ultraviolet light (UVA) and various doses of protoporphyrin (PP) on the release of histamine from rat peritoneal and cutaneous mast cells. We also correlated these results with morphologic characteristics and viability of the cells. PP at a dose of 30 ng/ml plus UVA-induced negligible histamine release from rat peritoneal mast cells (RPMC), but was able to suppress the ability of the cells to release histamine in response to subsequent exposure to the calcium ionophore A23187, compound 48/80, or the combination of Ag and IgE. This functional change was associated with an increase in cell size, and cell lysis that gradually occurred during 24 h in culture. PP at a dose of 3 ng/ml plus UVA also significantly inhibited secretogogue-induced histamine release from rat peritoneal mast cells, but this dose was not associated with significant changes in morphology or viability. These various effects of PP plus UVA were also observed with mast cell preparations obtained by the enzymatic dispersion of rat skin. The suppression of secretogogue-induced histamine release in rat peritoneal mast cells treated with PP (3 ng/ml) and UVA could not be reversed by culturing the cells in the dark for 24 h in the absence of PP. Unlike the direct cytotoxic histamine releasing action of high doses of PP plus UVA, the suppressive effect of low PP doses could not be inhibited by catalase, but could be reduced by the absence of calcium. Our results indicate that PP plus UVA has dual effects on mast cells, apparently involving distinct mechanisms. This implies the possibility that PP and UVA at appropriate doses could be used in photochemotherapy of mast cell-mediated skin diseases.
 ...
PMID:Dual effects of protoporphyrin and long wave ultraviolet light on histamine release from rat peritoneal and cutaneous mast cells. 169 61

Mast cells are widely distributed in perivascular connective tissues, especially in areas of active tumor growth and vascular reactivity. Incubation of metabolically [35S]O4 = -labeled subendothelial extracellular matrix (ECM) with lysates of bone marrow-derived mouse mast cells (BMMC) resulted in extensive degradation of heparan sulfate (HS) into fragments 5 to 6 times smaller than intact HS side chains. A much lower activity (seven- to eightfold) was expressed by intact BMMC incubated in contact with the ECM. These fragments were not produced in the presence of heparin, were sensitive to deamination with nitrous acid, and resistant to further degradation with papain or chondroitinase ABC. These results indicate that an endoglycosidase (heparanase) is involved in BMMC-mediated degradation of HS in the subendothelial ECM. Heparanase activity was not detected in medium conditioned by cultured BMMC, or in lysates of Ableson transformed BMMC and rat basophilic leukemic (RBL) cells. Both heparanase and beta-hexosaminidase, a mast cell granule enzyme, were released on degranulation of BMMC induced by the calcium ionophore A23187, or by exposure to IgE-Ag, suggesting that heparanase is localized in the cell granules. Under these conditions, less than 5% of the cellular content of lactate dehydrogenase were released. Degradation of the ECM-HS by the mast cell heparanase and the associated release of HS-bound endothelial cell growth factors that are stored in ECM (Vlodavsky et al, Proc Natl Acad Sci USA 84:2292, 1987; Bashkin et al, Biochemistry 28:1737, 1989) may play a role in the proposed mast cell-mediated stimulation of neovascularization.
 ...
PMID:Degranulating mast cells secrete an endoglycosidase that degrades heparan sulfate in subendothelial extracellular matrix. 169 99

We have previously found that antigenic stimulation of mast cells in the guinea pig superior cervical ganglion leads to membrane depolarization of principal neurons and a long-term increase in the efficacy of ganglionic transmission. In this study experiments were conducted to discern the histological, immunological and pharmacological characteristics of the mast cells within the superior cervical ganglion. Mast cells within the superior cervical ganglion could be stained with toluidine blue or berberine sulfate, the latter indicating that heparin-like molecules were present in the granules. Stainable mast cells were distributed throughout the ganglion with no gross evidence of regional localization. The number of mast cells stained with toluidine blue was reduced significantly (P less than 0.01) in contralateral ganglia that had been exposed to the sensitizing antigen (ovalbumin), indicating antigen-induced degranulation. The superior cervical ganglion contained 208 +/- 6 picomole of histamine (mean +/- SEM, n = 66). Ovalbumin evoked the release of histamine from the superior cervical ganglion in a concentration-dependent fashion. At maximally effective concentrations, ovalbumin released 33 +/- 2% of the total histamine stores (mean +/- SEM, n = 61). Similar values were obtained with antigen-challenged stellate ganglia. A temperature of 37 degrees C and an extracellular calcium concentration of 1 mM was required to elicit optimal antigen-induced responses. In addition to releasing histamine, antigenic stimulation of the ganglion resulted in a 3- to 5-fold increase in the synthesis and release of arachidonic acid metabolites including peptidoleukotriene, thromboxane B2, prostaglandins (PG) E2, F2 alpha, D2, the PGD2 metabolite 9 alpha 11 beta-PGF2, and the prostacyclin metabolite 6-keto PGF1 alpha. Various putative mast cell secretagogues were examined for their ability to activate the superior cervical ganglion mast cell, as indicated by evoked histamine release. In contrast to rat peritoneal mast cells, high concentrations of substance P, compound 48/80, and nerve growth factor failed to stimulate the ganglion mast cells. Preganglionic nerve stimulation, electrical field stimulation of axons and cell bodies, or depolarizing concentrations of potassium chloride also failed to activate the superior cervical ganglion mast cells. These results suggest that substances released by membrane depolarization do not influence the function of the resident mast cells. The results demonstrate that the mast cells within sympathetic ganglia can be actively sensitized to respond to specific antigen. These mast cells are similar to lung parenchymal mast cells with respect to histological, immunological and pharmacological characteristics...
 ...
PMID:Mast cells in the guinea pig superior cervical ganglion: a functional and histological assessment. 169 91

In accordance with our previous results, a marked release of histamine (HA) from rat peritoneal mast cells was initiated by 150 mM KCl in the absence of extracellular Ca2+. This release could be reduced by 20-60 mM tetraethylammonium (TEA) or tetramethylammonium (TMA), the non-selective K(+)-channel blockers, Ouabain, the general inhibitor of (Na+ + K+) ATP-ase, failed to produce any changes in this release. The action of TEA discriminated between the initiation of HA release evoked by different agents, producing a blockade of the K(+)-induced but not the 48/80-stimulated HA release. In total, these data suggest the presence of TEA/TMA-sensitive K(+)-channels in the mast cell membrane and their involvement in one of the possible pathways for the initiation of HA release.
 ...
PMID:Inhibition of potassium-induced release of histamine from mast cells by tetraethylammonium and tetramethylammonium. 169 36

In this study data are presented on the kinetics of changes in malondialdehyde content (MDA), lipoxygenase activity (LO), superoxide dismutase activity (SOD), glutathione peroxidase activity (GSH-Px) and glutathione reductase activity (GSSG-Red) during the course of histamine secretion from rat mast cells. Both receptor-mediated (antigen, polymyxin B, compound 48/80) and non-receptor (the calcium ionophore A23187) stimuli of mast cell activation were investigated. A similar alteration in all the studied indices was observed after challenge with receptor-mediated stimuli. The earliest event was a decrease in SOD-activity, which coincided with the increase in histamine secretion. SOD-activity then gradually increased above the baseline levels. Similar changes in GSSG-Red- and GSH-Px-activities were also observed. The increase in MDA content occurred slightly later. Challenge with the calcium ionophore A 23187 did not cause a reduction in SOD-activity, only the increase in activity was observed. Histamine release induced by all stimuli was accompanied by a marked elevation in enzymatic peroxidation (LO-activity). Diethyldithiocarbamate (DTC), which inhibits SOD, not only blocked the enzyme activity but also caused a dose-dependent inhibition of histamine release and an inhibition of the elevation of enzymatic peroxidation in mast cells challenged with compound 48/80.
 ...
PMID:Kinetics of oxygen metabolism indices in the course of histamine secretion from rat mast cells. 169 69

The immediate skin test due to interaction between allergen and mast cell bound IgE is one of the cornerstones in the clinical allergy workup. The release of histamine and other mediators from basophils and mast cells depends on the influx of Ca2+ into these cells when stimulated. The aim of this study was to evaluate the effect of common therapeutic doses of nifedipine (NFD), one of the calcium channel blockers, on the allergen skin tests. We prick tested 23 grass sensitive individuals with 7 different grass pollens at three times: at basal conditions (T0), 30 min. after having taken 20 mg of NFD s. l. (T1), and 17 of them after a week of receiving twice a day 20 mg of a NFD retard form (T2). The wheal surface obtained for each substance (allergen, histamine) at T0 was considered as basal value and compared with the one obtained at T1 and T2 for the same substance by the Wilcoxon's test. We found a significant increase in the wheal surfaces, both with allergen and histamine, at T1 and T2. In contrast to what could be expected, common therapeutic doses of NFD produce a discrete but statistically significant increase of the PT. Factors such as arteriolar vasodilation could be implicated. The increase of the allergen prick test and the increase of the histamine prick test both at T1 and T2 were not statistically different. Therefore, we do not think it necessary to stop NFD before allergen skin testing.
 ...
PMID:Effect of nifedipine on skin prick tests. 169 76

Histamine H1-antagonists inhibit the weal-and-flare responses to the intradermal injection of platelet activating factor (PAF) in humans, and PAF response is reduced in histamine-depleted skin sites. This indicates that mast cell histamine release is likely to be the mechanism of this response. We have therefore studied the interaction of PAF with cutaneous mast cells by observing whether it releases histamine directly from human dispersed foreskin mast cells, potentiates the activity of known mast cell stimulants or liberates histamine releasing factors (HRFs) from human platelets and leucocytes to release mast cell histamine by an indirect mechanism. At a concentration of 100 microM both PAF C18 and PAF C16 caused near maximal release (83.5 +/- 4.3% and 88.2 +/- 4.5% respectively) of the total histamine content of the cell. This release was not inhibited in the absence of extracellular Ca2+, by the lack of metabolic energy or in the presence of the PAF antagonists WEB 2086 (100 nM-3 microM) or BN 52021 (100 nM-10 microM). These results indicate a cytotoxic mechanism of histamine release by PAF 100 microM. PAF (10 nM-1 microM) failed to potentiate the mast cell-stimulating activity of anti-IgE, calcium ionophore A23187 or substance P and it did not induce the release of HRFs for skin mast cells when incubated with platelets and leucocytes in concentrations up to 1 microM.
 ...
PMID:Platelet activating factor does not release histamine from human dispersed cutaneous mast cells. 169 68


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