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)

Tryptase, a mediator secreted by human mast cells during immediate reactions, has demonstrated effects on several pathways in vitro. This enzyme can rapidly inactivate fibrinogen and, as a complex with heparin, may prevent coagulation that may otherwise occur when plasma enters tissues at sites of immediate reactions. Tryptase may also activate prostromelysin, which in turn activates latent collagenase. When canine pulmonary smooth muscle is incubated with canine tryptase, the contractile response to histamine is increased. Tryptase, quantifiable in complex biologic fluids by immunoassay, can serve as a specific indicator of mast cell involvement in certain clinical settings. For example, after bee sting--induced anaphylaxis, tryptase levels in the blood peak at approximately 1 hour, then decline with a half-life of approximately 2 hours. Additionally, elevated tryptase levels in bronchoalveolar lavage fluid of asymptomatic, atopic persons with asthma suggest ongoing mast cell activation, which may relate to adenosine hyperresponsiveness and a persistence of bronchial hyperreactivity. Tryptase levels in bronchial lavage fluid of atopic patients with asthma rise markedly after endobronchial allergen challenge but not after an exercise challenge, suggesting a lack of mast cell involvement in the latter condition.
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PMID:Tryptase, a mediator of human mast cells. 222 22

1. Inhaled adenosine and its parent nucleotide, adenosine 5'-monophosphate (AMP) provoke bronchoconstriction in atopic and asthmatic individuals but not in normal subjects. 2. In clinical studies, histamine H1-receptor antagonists, cyclo-oxygenase inhibitors and the mast cell 'stabilising' drugs, sodium cromoglycate and nedocromil, protect against the effects of adenosine bronchoprovocation suggesting the involvement of secondary mast cell mediator release. 3. Adenosine and its analogues potentiate histamine and leukotriene release from mast cells activated by other stimuli in vitro, and may also increase net mediator release from mast cells by counteracting the inhibitory effect of circulating adrenaline. 4. Although adenosine fulfils many of the criteria required for a mediator in asthma, its importance is not fully understood, and the mechanisms by which it provokes bronchoconstriction in asthmatic subjects is far from concluded. 5. Two possibilities are that either adenosine acts directly on luminal mast cells to upregulate histamine secretion, or it acts to initiate neuronal reflexes which stimulate histamine release indirectly and possibly activate peptidergic and/or cholinergic pathways.
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PMID:Adenosine bronchoconstriction in asthma: investigations into its possible mechanism of action. 226 11

The allergic bronchoconstriction in guinea pigs has been attributed mainly to the release of mast cell mediators. Histamine has been involved in the first minutes of the anaphylactic reaction and new-formed compounds in the subsequent response. In this asthma model the vagal influence has been sparsely investigated. In the present work we evaluated the pharmacological modification of the acute allergic bronchoconstrictor response in guinea pigs sensitized to ovalbumin through aerosol exposure. Pyrilamine (20 micrograms/kg), diethylcarbamazine (a lipoxygenase inhibitor, 10 mg/kg) and dexamethasone (4 mg/kg) each reduced the antigen-induced bronchoconstriction throughout the 30 min studied. Indomethacin (3.1 mg/kg) did not modify the response to the antigen. Atropine (2 mg/kg) plus bilateral vagotomy also diminished this response from 5 min onward. On the other hand, from 5 min ahead pyrilamine-resistant bronchoconstriction was partially inhibited by dexamethasone, and it was almost completely blocked during all of the response when atropine plus bilateral vagotomy were added to dexamethasone. Dipyridamole (an inhibitor of the adenosine uptake, 0.4 mg/kg) enhanced the bronchoconstriction, though this was significant only in the 2-5 min time-interval of the response. These results suggest that histamine and vagal influence play an important role in the whole response to antigen, that other mediators, probably leukotrienes, participate in this response from 5 min onward, and that adenosine could exert a potentiation effect on this response.
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PMID:Pharmacological characterization of mediators and vagal influence in the acute allergic bronchoconstriction in guinea pigs. 228 Jul 95

The regulatory effects of various endocrine factors on allergic processes have been widely studied. The clinical importance of hyperthyroidism in asthma and in chronic urticaria has been demonstrated in several cases. These observations may be attributed to modulatory effects of thyroid hormones on mast cell releasability and/or on other target organs as blood vessels. To evaluate the effects of thyroid hormones on mast cell releasability and on the cutaneous vasculature, we analyzed the wheal and flare response to compound 48/80, to codeine, and to histamine in patients with hyperthyroidism and in a control group. No significant difference was found between the two groups. We could not demonstrate any in vivo effect of the thyrotoxic state on the cutaneous response to these substances.
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PMID:Cutaneous responses to histamine, compound 48/80 and codeine in patients with hyperthyroidism. 230 20

Inhaled furosemide has been recently demonstrated to inhibit the bronchoconstrictive effects of exercise, ultrasonically nebulized distilled water, and antigen challenge. The presumed mechanism of action of these challenges is through mast cell degranulation. We report on the effect of inhaled furosemide on cold-air hyperventilation challenge (CAHC) and methacholine challenge. We studied 10 subjects with mild to moderate asthma in a double-blind, placebo-controlled, crossover study. Inhaled furosemide did not affect FEV1 in the hour after inhalation, and there was no significant difference between placebo or furosemide on the dose of methacholine causing a 20% fall in FEV1. Our results demonstrated inhaled furosemide significantly attenuated the bronchoconstrictive effect at 6 and 9 minutes after CAHC (p less than 0.05 and 0.029, respectively) when furosemide was compared to placebo and approached significance at 12 and 15 minutes after CAHC (p = 0.052 and 0.56, respectively). Inhaled furosemide attenuates CAHC but does not effect methacholine-induced bronchoconstriction.
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PMID:Effect of inhaled furosemide on the bronchial response to methacholine and cold-air hyperventilation challenges. 233 65

Corticosteroids, used in low to moderate doses for short time intervals, do not suppress immediate percutaneous skin test responses to allergens, compound 48/80, or histamine. During routine skin testing, in our clinic, intradermal injection of codeine (1 mg/ml) and histamine (0.02 mg/ml) are used as positive controls. We had noted that responses to codeine but not histamine are decreased in some patients with asthma who had been receiving prolonged corticosteroid therapy. Therefore, we retrospectively compared skin test responses to codeine and histamine between 25 adult subjects with asthma receiving steroids (group I) and 25 age-matched control subjects (group II). In group I, the mean wheal diameters, induced by codeine but not histamine, were significantly less than diameters in group II. This decreased skin test reactivity to codeine was not due to effects of theophylline also taken by group I subjects, since the skin test reactions of other subjects with asthma, treated with theophylline but not steroids (group III), were not significantly different from reactions in group II. We conclude that prolonged courses of corticosteroids do not appear to alter histamine-induced vascular reactivity in skin but may affect cutaneous mast cell responses by an undefined mechanism.
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PMID:Skin reactivity to codeine and histamine during prolonged corticosteroid therapy. 238 46

Calcium entry blocking drugs attenuate antigen-induced bronchoconstriction in asthma which is mast cell mediated. We have investigated the effects of two calcium uptake blockers, nicardipine and nifedipine on histamine secretion from human mast cells dispersed from lung and tonsillar tissue. Mast cells were activated for secretion with anti-human IgE or calcium ionophore, A23187. Nicardipine and nifedipine caused a concentration-related inhibition of IgE-dependent histamine release from both lung (IC30 10 microM and 4.4 microM) and tonsillar (IC30 21 microM and 47 microM) mast cells. Nicardipine and nifedipine also inhibited mast cell histamine release induced by A23187 with IC30 values of 14 microM and 67 microM for lung and 15 microM and 30 microM for tonsillar mast cells. In the absence of drugs, increasing the extracellular calcium concentrations from 0.2 to 5 mM caused a concentration related increase in IgE-dependent histamine release from tonsillar mast cells. Both nicardipine and nifedipine (50 microM) displaced the concentration-effect curve to the right. Nicardipine (0.01-100 microM) caused a concentration related inhibition of rat kidney histamine methyltransferase activity used in the radioenzymatic assay of histamine (ki of 7.5-12 microM) whereas nifedipine was only a weak inhibitor. Nicardipine also interfered with the spectrofluorimetric assay after exposure to ultraviolet light. These observations demonstrate that nicardipine and nifedipine inhibit IgE-dependent and ionophore stimulated mediator secretion from human mast cells. The lack of stimulus-related specificity and the high drug concentrations required suggest that classical calcium channel blockade is not responsible for inhibition of mast cell mediator release. Furthermore, we suggest that inhibition of mast cell mediator release is unlikely to be the mechanism by which these drugs alleviate asthma.
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PMID:Inhibition of histamine release from dispersed human lung and tonsillar mast cells by nicardipine and nifedipine. 240 45

There is now compelling evidence to incriminate bronchial mast cells in the pathogenesis of bronchoconstriction of allergic asthma. Human mast cells isolated from lung tissue or bronchoalveolar lavage release histamine and generate eicosanoids upon IgE-dependent activation. In this paper we present data that raise doubts about the significance of phospholipid methylation in IgE-dependent activation-secretion coupling and provide evidence that drugs such as 3-deazaadenosine inhibit mediator secretion by inhibiting phosphodiesterase, in addition to inhibiting putative methylation pathways. Activation of human mast cells and basophils also stimulates adenylate cyclase to increase levels of cyclic AMP, which, on the basis of pharmacological manipulation with purine nucleosides, we believe is involved in the progression of the secretory response. Human lung cells also generate both cyclo- and lipoxygenase products of arachidonate upon Ca++-dependent stimulation with complex interactions occurring between these pathways in the presence of the leukotriene inhibitor, Piriprost. The role of mast cells in the immediate airway response to inhaled allergens in asthma was demonstrated by showing an interaction between nonspecific bronchial reactivity and mast cell reactivity in predicting the airway response upon antigen inhalation. Further confirmation of this concept was obtained by showing an inverse relationship between the release of histamine and neutrophil chemotactic factor (NCF) into the circulation induced by antigen challenge, and nonspecific airway reactivity. The identification of significant increases in circulating mediators following antigen provocation of patients with seasonal asthma enabled the effects of drugs used in the treatment of asthma to be compared on airway calibre and mast cell mediator release. Sodium cromoglycate partially inhibited the airway and plasma histamine responses with antigen, but totally inhibited the increases in NCF. Salbutamol completely inhibited all responses, while ipratropium bromide, which produced the same bronchoconstriction as achieved with salbutamol, had no effect. The potent H1-antagonist astemizole partially inhibited bronchoconstriction without affecting histamine release. Antigen provocation produced a significant increase in circulating levels of the 13,14-dihydro-15-keto metabolite of PGF2 alpha which could originate from mast cell-derived PGD2. In both retrospective and prospective studies, a close relationship was shown between nonspecific bronchial reactivity and resting airway calibre in asthma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Relationship between mediator release from human lung mast cells in vitro and in vivo. 240 26

Although their precise mechanisms of action are undefined, the usefulness of CCS in the treatment of asthma is unquestioned. It is clear that they act at multiple sites. Among the general actions of CCS felt to be applicable to asthma are their ability to facilitate beta-adrenergic responsiveness and to suppress inflammation. More specific actions relevant to asthma are their inhibition of eicosanoid formation (e.g., reduction in leukotriene formation), prevention and reversal of LPR (probably through CCS anti-inflammatory effects), and reduction in mucus secretion. Actions that have not yet been clarified but that may be useful include possible reductions in airway hyperreactivity (or at least the prevention of increases in reactivity superimposed upon overreactive airways) and suppression of basophil (but not mast cell) mediator release.
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PMID:Mechanisms of glucocorticosteroid action in bronchial asthma. 241 Apr 76

Calcium ions participate in the pathogenesis of asthma. Increased cytosolic concentrations of free Ca2+ must develop to trigger smooth muscle contraction, mast cell mediator release, mucous gland secretion, vagal nerve activity, and the movement of inflammatory cells into the walls of the airways. Recent interest has centered on the possibility that Ca2+ antagonists might be useful in the treatment of asthma. Evidence now exists that airway smooth muscle contraction and mast cell and basophil mediator release may be inhibited by the calcium channel blockers nifedipine and verapamil. Other experiments indicate that these drugs may interfere with EIA and bronchoconstriction provoked by cold air and methacholine, for example. CaM antagonists may also interfere with smooth muscle contraction and mediator release. It is possible that more specific calcium antagonists, both Ca2+ channel blockers and CaM-active compounds, will be developed and find use as effective antiasthmatic agents.
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PMID:Calcium antagonists and asthma. 241 Apr 77


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