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  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study provides evidence for a number of calcium pools important in histamine secretion from the mast cell. Firstly, calcium loosely bound to the cell membrane, and in rapid equilibrium with the extracellular environment, may be utilized for histamine release induced by most secretagogues. Secondly, all inducers are able to mobilize deeply buried or internal stores of calcium to initiate exocytosis. Finally, calcium bound to regulatory sites in the membrane may modulate the secretory process. Removal of calcium from the latter sites by brief treatment with chelating agents markedly enhances the secretory response in the absence of extracellular calcium, probably by facilitating the mobilization of bound stores of the ion. Saturation of these sites in the presence of excess calcium inhibits the release process and may restrict influx of the cation.
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  • 2
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of various histamine liberators and inhibitors on isolated rat peritoneal and pleural mast cells have been compared. The pleural cells showed an increased reactivity to challenge with antigen following passive, but not active, sensitization and were more responsive to challenge with anti-IgE. Phosphatidyl serine enhanced the secretion from both cell types. Peritoneal and pleural cells exhibited virtually identical responses after treatment with chemical secretagogues in the presence of exogenous calcium, but the peritoneal cells were significantly more reactive to stimulation with basic inducers in the absence of the cation. Anaphylactic histamine secretion was comparably inhibited by a number of anti-allergic drugs but the peritoneal cells were rather more sensitive to inhibition by dibutyryl cyclic AMP. These results are discussed in terms of the general functional heterogeneity of mast cells from different sources.
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  • 3
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A method is described for the isolation of mast cells from the mucosa of the small intestine of rats infected with the nematodeNippostrongylus brasiliensis. The cells release histamine on challenge with IgE-directed ligands and calcium ionophores but, in contrast to rat peritoneal mast cells, are refractory to the action of basic secretagogues. The mucosal and peritoneal cells also differ markedly in their sensitivity to particular anti-allergic drugs. These results further emphasize the functional heterogeneity of mast cells from different sources.
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  • 4
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The calcium antagonists verapamil and nifedipine inhibited histamine release induced from rat peritoneal mast cells by a number of secretory stimuli. However, the concentrations required were much higher than those active in smooth muscle preparations. The inhibition was unaffected by elevated levels of external calcium and the drugs prevented release in the absence of added calcium. The novel calcium antagonist, PY 108-068, had no effect on histamine secretion from mast cells. These results suggest that calcium channels in the mastocyte may differ from those in smooth muscle and that at concentrations required to inhibit secretion, verapamil and nifedipine may have non-specific stabilizing effects on the mast cell membrane.
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  • 5
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A method has been developed for the dispersion of guinea-pig lung into its component cells using the proteolytic enzyme collagenase. The procedure typically yielded 5×106 mast cells per g of tissue with a recovery of histamine ofca. 20%. The mast cells comprised 2% of the total nucleated cells, had a histamine content of 1–2 pg per cell and exhibited a low spontaneous release of the amine (ca. 6%). In contrast to the rat peritoneal mast cell, guinea-pig lung mast cells were refractory to the action of compound 48/80, peptide 401 (MCD-peptide), dextran and Concanavalin A. However, the cells released histamine on antigenic challenge following active sensitization and dose-dependent histamine secretion was also produced by the ionophores A23187, ionomycin and Br-X537A. These results further emphasize the functional heterogeneity of mast cells obtained from different species and tissues.
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  • 6
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The lipid phosphatidylserine (PS) markedly potentiated anaphylactic histamine secretion from isolated rat peritoneal mast cells in the presence of extracellular calcium ions. The compound correspondingly reduced the inhibitory effect of disodium cromoglycate on the secretion induced by optimal concentrations of antigen. However, at a constant concentration of PS, suboptimal amounts of antigen were effectively inhibited by the drug. The inhibitory power of cromoglycate increased as the concentration of antigen was decreased and the corresponding control release of histamine declined. At control values similar to those observed without addition of PS, the drug inhibited secretion to a similar extent as in the absence of the lipid. At given concentrations of PS and antigen, the potency of the drug increased with decreasing degrees of sensitization of the experimental animals. These effects are not likely to reflect a direct interaction between the drug and PS since increasing the concentration of the lipid by one hundred-fold did not affect the inhibitory effect of the chromone. Further, the latter was essentially equiactive in the presence and absence of PS in calcium-free media, conditions under which the lipid did not enhance histamine release. These results are discussed in terms of the proposed modes of action of PS and cromoglycate.
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  • 7
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The novel calcium ionophore chlortetracycline (CTC) induced histamine secretion (≤90%) from isolated rat peritoneal mast cells in a pH and dose-dependent fashion. The process was dependent on exogenous calcium ions and was inhibited by extremes of temperature and metabolic blockers. The release was rapid, being essentially complete within 1 min, but the half-life of the process varied inversely with the concentration of the ionophore. In contrast to receptor-mediated ligands, but in keeping with other ionophores, the activated state induced by CTC did not decay with time. The secretion was effectively inhibited, according to the concentration of the ionophore, by disodium cromoglycate and other anti-allergic or cyclic AMP-active drugs. These results confirm our previous contention that these agents do not act on receptor-mediated calcium-channels. CTC induced a significant (≤50%) release of histamine from enzymically dispersed rat mesenteric mast cells but was essentially inactive against isolated mast cells from the mesentery or lung of the guinea-pig. These results extend our former observations on the functional heterogeneity of mast cells and show that, in common with other secretagogues, ionophores may exhibit selectivity in their mode of action.
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  • 8
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of various inhibitors and anti-allergic drugs on histamine secretion from peritoneal mast cells of the rat, mouse and hamster have been compared. Phosphodiesterase inhibitors, cAMP analogues andβ-adrenoceptor agonists variously blocked release of the amine from all three cell types. The mouse cells were rather less sensitive to the former agents than those of the rat and hamster. Disodium cromoglycate inhibited histamine secretion from rat peritoneal mast cells, was less active against the hamster cells and completely ineffective against those of the mouse. Other chromones showed varied patterns of differential reactivity but phloretin and the flavonoid quercetin were essentially equiactive against all three cell types. The tetrazoles AH 9679 and doxantrazole prevented histamine release in each case but were significantly less active against the mouse cells. These results further emphasize the functional heterogeneity of mast cells from different sources.
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  • 9
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract d-Tubocurarine (dTc) released histamine in non-cytotoxic fashion from peritoneal mast cells of the rat, mouse and hamster. The response was similar to that evoked by other cationic liberators such as compound 48/80 and polylysine in that it was extremely rapid and enhanced by calcium-deprivation at suboptimal concentrations of secretagogue. Tissue mast cells obtained by enzymic dissociation of the heart, lung and mesentery of the rat and guinea pig were unreactive or hyporesponsive to the effect of dTc. The compound liberated only very small amounts of histamine from isolated preparations of perfused guinea pig heart but significantly increased the rate and contractility of the heart. These results are discussed in terms of the general functional heterogeneity of mast cells from different locations.
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  • 10
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of a range of antihistamines and related compounds on mast cells from a number of different locations have been investigated. The drugs had a dual action on all the cell types examined: at high concentrations they induced histamine release while at low concentrations they inhibited the secretion of the amine evoked by antigen. The relative potencies of the various compounds in both evoking and preventing histamine release varied from one mast cell to another. In total, these studies then further emphasise the functional heterogeneity of mast cells from different locations.
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