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)

Protamine sulfate, known for a long time as a histamine releaser, was labeled with a fluorescent dye (FITC). This conjugate was shown to stain selectively the mast cell fraction of rat peritoneal cells. Within a few seconds, the protamine was found inside the cells. Although the cells had lost their histamine completely, no granules were found outside the cells. In the electron microscope, the protamine treated mast cells showed a loss of the electron density of their granules, a vacuolization, and other signs of histamine release. Evidence for a direct connection between the vacuoles and the extracellular fluid was gained by incubating mast cells in FITC-labeled human serum albumin followed by the addition of unlabeled protamine. After washing, the fluorescence was found to be located inside the cells, demonstrating an influx of the FITC-HSA under the influence of protamine. The protamine-induced release reaction is increased after addition of Ca2+, reduced by lowering the temperature, addition of 2-deoxyglucose, or cytochalasin B. Disodium cromoglycate also diminished the histamine release in a dose dependent manner. Protamine did not induce a loss of lactate dehydrogenase from the mast cells. The release reaction is mediated by the cell membrane, as shown by the releasing activity of insolubilized protamine. We conclude that the protamine-induced release is a non-cytotoxic reaction, fulfilling some criteria of the anaphylactic histamine release.
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PMID:[Mode of action of protamine sulfate on histamine secretion in the rat mast cells]. 616 92

Disodium cromoglycate has been reported to benefit some patients with active ulcerative colitis. We have investigated the effect of cromoglycate in high dose on rectal mucosal mast cell degranulation (assessed indirectly by measurement of mucosal histamine release, using in vivo rectal dialysis, and the eosinophil content of the rectal inflammatory exudate) and on disease activity in eight patients in relapse. Although cromoglycate (1600 mg by mouth daily for 2 weeks) did not affect histamine release, it reduced (P less than 0.05) the eosinophil content of the exudate towards normal. Stool frequency also fell (P less than 0.05) but other aspects of bowel habit, sigmoidoscopic appearance, rectal mucosal potential difference and electrolyte transport were unaltered. Pre-treatment values of histamine release and eosinophil exudation could not be used to predict the response to cromoglycate. The reduction in eosinophil exudation produced by the drug could be due to inhibition of mast cell release of chemotactic factors other than histamine; the therapeutic effect of cromoglycate was unimpressive.
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PMID:The effect of disodium cromoglycate on rectal mucosal histamine release, eosinophil exudation and disease activity in active ulcerative colitis. 617 53

Disodium cromoglycate and compounds which elevated levels of cyclic AMP in the mast cell variously inhibited cytotoxic histamine release induced by the surface active agents melittin, Tween 20 and Triton X-100. These results are inconsistent with the postulated effects of the drugs on receptor mediated calcium channels and alternative explanations of their action are considered.
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PMID:Effect of disodium cromoglycate and cyclic AMP-active drugs on cytotoxic histamine release from rat mast cells. 618 90

Challenge of rat peritoneal mast cells with anti-rat IgE induces a similar pattern of protein phosphorylation to that already reported for compound 48/80. Rapid phosphorylation of a mast cell protein, mol. wt 78,000, is induced by sodium cromoglycate and several chemically related anti-allergic agents in the absence of any challenge. Phosphorylation of this protein reflects their potency in inhibiting anti-IgE-induced histamine release. Compounds which inhibit histamine release by elevating intracellular cAMP levels do not induce phosphorylation. However, dibutyryl-cGMP induces phosphorylation of the 78,000 mol. wt protein in the absence of any challenge, at concns which inhibit IgE-dependent histamine release. Sodium cromoglycate appears to activate an endogenous control mechanism for switching off mediator release using a mechanism mediated by cGMP.
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PMID:Phosphorylation of a mast cell protein in response to treatment with anti-allergic compounds. Implications for the mode of action of sodium cromoglycate. 640 82

The effect of ketotifen was compared with that of clemastine and chlorpheniramine, known antihistamines, and sodium cromoglycate, a drug considered to have mast cell "stabilizing' properties on histamine and allergen wealing reactions in human skin, in random order, double-blind, placebo controlled studies. Ketotifen was significantly more potent in the inhibition of both histamine (P less than 0.001) and allergen (P less than 0.001) skin wealing reactions than either clemastine or chlorpheniramine. Sodium cromoglycate had no significant effect on either histamine or allergen skin wealing reactions in any of the concentrations tested. However ketotifen, like clemastine, had a significantly greater inhibitory effect on histamine than on allergen induced weals (P less than 0.001) and both drugs were shown to act as competitive antagonists of histamine. Ketotifen has been shown to be a potent anti-histamine but there is no evidence from these in vivo studies to suggest that it has any additional inhibitory activity on release of mediators from mast cells in human skin.
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PMID:A comparison of the in vivo effects of ketotifen, clemastine, chlorpheniramine and sodium cromoglycate on histamine and allergen induced weals in human skin. 640 71

The actions of F 1865 (ethyl 4' methoxy 4 phenyl thiazolyl 2 oxamate), an inhibitor of the release of histamine from mast cell, desonide, a corticosteroid, mepyramine maleate, an anti-H1 antihistaminic, and disodium cromoglycate were compared after cutaneous application in various experimental models of allergy and inflammation. F 1865 decreased IgE- and IgG-dependent passive cutaneous anaphylaxis in rats at doses having no effect on histamine- and serotonin-induced capillary permeability. Disodium cromoglycate showed the same activity spectrum, but its action was only found after intradermal application. The reduction of cutaneous anaphylaxis by desonide was found parallel to its inhibition of histamine effects, and to a lesser extent of serotonin effects. In the case of mepyramine, the antiallergic effect may be explained by its antihistaminic action. Desonide was highly active on cantharidin-induced non-immune inflammation and on non-immune and delayed hypersensitivity reactions induced by picryl chloride in mouse ear. Although far less active than the corticosteroid, F 1865, mepyramine and disodium cromoglycate did reduce the three types of reactions in mice. This evidenced a part played by histamine in such inflammations. Then it is likely that the inhibition of histamine release by F 1865 plays an important part in the effect of the compound observed in the various inflammations studied. However we cannot exclude actions against other mediators involved in these reactions.
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PMID:[Comparative antiallergic and anti-inflammatory action of F1865, mepyramine maleate, desonide and disodium cromoglycate after cutaneous administration]. 642 68

An immediate hypersensitivity reaction with mast cell degranulation may be of importance in the pathogenesis of ulcerative colitis. Cromolyn sodium stabilizes the mast cell membrane, and thus could have potential benefit in the treatment of this disease. The few clinical studies published to date are difficult to interpret, and have not established the therapeutic benefit of cromolyn sodium in ulcerative colitis.
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PMID:Cromolyn sodium in the treatment of ulcerative colitis. 677 11

We used pharmacologic and histologic techniques to investigate the role of mast cells in the mediation of hypoxic pulmonary vasoconstriction in conscious sheep. Breathing a hypoxic gas mixture (13%, 02, 87% nitrogen) caused hypoxic pulmonary vasoconstriction (HPV) with increases in mean pulmonary artery pressure and pulmonary vascular resistance by 97 and 90%, respectively. Intravenous pretreatment with the mast cell membrane stabilizing agent cromolyn sodium (3 mg/kg/min) completely blocked HPV, whereas the H1-histamine receptor antagonist chlorpheniramine, alone or in combination with the H2-receptor antagonist metiamide and the prostaglandin synthetase inhibitor indomethacin, failed to prevent HPV. Cromolyn sodium failed to modify the pulmonary pressor response to infusions of norepinephrine (alpha-agonist), tyramine (catecholamine-releasing agent), and histamine, indicating the specificity of cromolyn sodium action on the mast cells. Electromicroscopic studies of pulmonary perivascular mast cells showed that a 90-min exposure to the hypoxic gas mixture reduced the total number of granules per mast cell to 75% of control. This was blocked by cromolyn sodium pretreatment. We conclude that in conscious sheep], HP[V is initiated by the liberation of a mast cell product (other than histamine) that either directly or indirectly causes pulmonary vasoconstriction.
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PMID:Hypoxic pulmonary vasoconstriction in conscious sheep: role of mast cell degranulation. 680 79

The mechanisms underlying water-induced bronchoconstriction are still not fully understood. Cholinergic reflexes and mast cell mediator release are currently believed to play an important pathogenetic role. In order to evaluate the relative contribution of each of these mechanisms, we studied the effect of ipratropium bromide (80 micrograms), a muscarinic antagonist, and sodium cromoglycate (20 mg), an inhibitor of mast cell mediator release, administered alone and in combination, in the prevention of bronchospasm induced by ultrasonic mist of distilled water (UMDW). Fifteen patients with documented atopic asthma and hyperresponsiveness to distilled water were selected for this randomized, placebo-controlled, double-blind study. Airway responses to pharmachological agents and bronchial challenge were measured by change in specific airways conductance (sGaw). Sodium cromoglycate had no effect on bronchial calibre, whilst ipratropium bromide and the combination of the two drugs produced a significant bronchodilation 30, 60 and 90 min after treatments. The maximal increase in sGaw (mean % +/- SD) was observed at 90 min: 63 +/- 28% and 58 +/- 22% after ipratropium bromide and the combined drugs respectively. UMDW (2, 4, 8, 16 ml water) caused a -36 +/- 19%, -42 +/- 19%, -49 +/- 18%, -56 +/- 15% mean % +/- SD fall in sGaw after placebo. Pretreatment with sodium cromoglycate abolished the bronchoconstriction to 2 ml (fall sGaw -5 +/- 23% NS) and significantly reduced the effect of 4 (-15 +/- 22%), 8 (-21 +/- 20%) and 16 ml (-24 +/- 18%) water.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of ipratropium bromide and/or sodium cromoglycate pretreatment on water-induced bronchoconstriction in asthma. 766 61

Heparin from degranulating mast cells influences a wide range of cellular and humoral reactions associated with allergic inflammation and asthma. Agents that inhibit mast cell degranulation may therefore compromise the moderating effects of heparin in the tissues and result in worsening inflammation and other associated pathology. This study measures heparin release from allergen-challenged human lung tissue and compares the effect of the mast cell stabilizing beta 2-agonists, salbutamol and fenoterol, and a non-beta 2-agonist, sodium cromoglycate, on the release of heparin. Pieces of lung tissue 2 to 3 mm3 were sensitized with high titer Dermatoaphagoides pteronyssinus-specific IgE serum and challenged with D. pteronyssinus allergen, with and without prior addition of salbutamol, fenoterol, or sodium cromoglycate. Dextran sulfate was added to the mixture to prevent the binding of heparin to tissue proteins. Heparin was released together with histamine after challenge. The mean and 95% confidence interval of prechallenge and postchallenge heparin concentrations in the lung tissue filtrates were 0.10 IU/ml (0.07, 0.12) and 0.24 IU/ml (0.17, 0.30), respectively (P < 0.001). Addition of the beta 2-agonists produced a mean inhibition of released heparin of 71% (50, 92), and 73% (55, 91), respectively. Sodium cromoglycate gave a 35% (20, 51) inhibition that was significantly less than that produced by the beta 2-agonists (P < 0.01). The beta 2-agonists salbutamol and fenoterol strongly inhibited heparin release from mast cells. The therapeutic use of mast cell stabilizing agents may therefore be potentially detrimental to the control of allergic inflammation and other associated pathologies.
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PMID:Effect of salbutamol, fenoterol, and sodium cromoglycate on the release of heparin from sensitized human lung fragments challenged with Dermatophagoides pteronyssinus allergen. 768 96


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