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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exercise induced bronchospasm (EIB) is a common clinical problem seen in most individuals with chronic asthma and in nearly half the allergic population. Bronchospasm is typically present 5-15 min after cessation of activity, with spontaneous resolution usually occurring within 20-60 min. The stimulus for EIB is apparently a combination of airway cooling and drying, which results in pulmonary mast cell mediator release. Bronchospasm is generally more severe if there is greater baseline bronchial hyperreactivity or higher intensity of exercise. The treatment of choice for EIB is preexercise administration of a beta-adrenergic agonist. Other useful therapies may include cromolyn, theophylline, calcium channel blockers, anticholinergics, and antihistamines. The crucial step for clinicians caring for these patients is making the diagnosis of EIB. The condition responds well to therapy, and treatment may allow for greater enjoyment of activity and enhanced athletic performance.
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PMID:Exercise-induced bronchospasm: epidemiology, pathophysiology, and therapy. 140 68

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.
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PMID:Effect of nifedipine on skin prick tests. 169 76

New therapeutic approaches in urticaria are presented with special respect to chronic and physical types including symptomatic dermographism, cholinergic urticaria, pressure and solar urticaria as well as vibratory angioedema. Clinical efficacies of several antihistamines (clemastine, astemizole, terfenadine, acrivastine, hydroxyzine, cimetidine), of ketotifen as a H1 receptor antagonist and mast cell stabilizer, of tricyclic antidepressant doxepin with H1 and H2 antagonist properties, of the calcium channel antagonist nifedipine, of topical corticosteroids and of the attenuated androgen danazol are presented. The data are specified by a detailed description of the design and particular conditions of the underlying study protocols.
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PMID:[The development of recent strategies in the treatment of urticaria as a result of clinically oriented research]. 197 Feb 7

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

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

Leukotrienes (LT) C4, D4, and E4 are major contributors to the pathobiology of human bronchial asthma. Therefore, it is likely that compounds that antagonize the action or inhibit the formation of LTs will be useful therapeutic agents. We have studied the effects of LT antagonists, 5-lipoxygenase inhibitors and selected standards in a model of LT-mediated allergic bronchospasm in guinea pigs. Sensitized animals were pretreated with mepyramine, indomethacin and propranolol to eliminate the influence of histamine, prostaglandins, thromboxanes and circulating catecholamines. In these animals, inhalation of antigen resulted in a bronchospasm consistent with a LT-mediated response that was slow in onset, of long duration and was inhibited by the selective LTD4, antagonists FPL-55712, LY-171,883 and ICI-198,615. ICI-198,615 was approximately 50-times more potent than FPL-55712 by the intravenous and intratracheal routes. However, of thirteen compounds known to inhibit 5-lipoxygenase and LT biosynthesis in vitro only phenidone, piriprost and AA-861 were active in this in vivo model. The allergic bronchospasm was inhibited by bronchodilators (e.g. PGE2, aminophylline and forskolin) and by some mast cell stabilizers, but was otherwise insensitive to other pharmacological classes of compounds including calcium channel blockers and antagonists of serotonin, acetylcholine and platelet-activating factor. This model seems useful and reasonably selective for the evaluation of new antianaphylactic compounds that are LT antagonists. The inactivity of many 5-lipoxygenase inhibitors in this model suggests they do not inhibit LT formation in vivo.
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PMID:The effect of leukotriene antagonists, lipoxygenase inhibitors and selected standards on leukotriene-mediated allergic bronchospasm in guinea pigs. 257 32

Recently there has been considerable controversy over the mechanism(s) by which intracellular Ca2+ is elevated when receptors for IgE on the surface of mast cells are aggregated by antigen. The central role played by calcium in the initiation of secretion from these cells has also been called into question. In a mast cell line which has been widely used to study stimulus-secretion coupling in non-excitable cells it is now clear that calcium is indeed important in the physiological response of the cells but that other intracellular messengers are also involved. In addition it has been shown that while the increase in intracellular Ca2+ probably originates from intracellular stores it can only be sustained by the influx of calcium across the plasma membrane. The nature of the Ca2+ permeability pathway has yet to be elucidated although a number of candidates for the calcium channel in mast cells have been proposed. Significant oscillations and spatial gradients of Ca2+ are often seen when the responses of individual antigen-stimulated cells are measured using digital imaging microscopy. The complexity of these responses highlights the importance of single-cell measurements in elucidating the relationship between IgE receptor activation, Ca2+ movements and exocytosis.
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PMID:Calcium: an important second messenger in mast cells. 269 5

This review will highlight recent advances in understanding the physiological role of calcium and effects of calcium channel blockers on pathogenetic factors in asthma, including airway smooth muscle contraction, mast cell degranulation and mucus secretion. A review of clinical studies with calcium channel blockers in asthma will also be presented.
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PMID:Calcium, calcium channel blockade and airways function. 287 71

The most reasonable first therapy for ambulatory asthmatic patients is regular use of a selective beta 2-adrenoreceptor agonist administered with a metered-dose inhaler. When asthma is of more than mild severity, a second agent that acts through a different pharmacologic pathway is added. Although theophylline has traditionally been this second agent, recent concerns about its safety have prompted increasing use of inhalational agents such as corticosteroids, anticholinergics and mast cell stabilizers as appropriate second-line therapy. The use of such combination regimens and newer strategies such as high-dose inhaled corticosteroid therapy will reduce the proportion of patients who require systemic corticosteroid therapy for adequate control of asthma. The use of combination inhalational therapy also has a role in the management of asthma in the emergency department, the combination of a nebulized adrenoreceptor agonist and a nebulized anticholinergic being more effective than either agent alone in acute, severe asthma. The role of newer xanthine derivatives, antihistamines, calcium channel blockers and selective anti-inflammatory agents remains investigational.
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PMID:Asthma: 2. Trends in pharmacologic therapy. 288 Jun 49

Verapamil is a calcium channel blocker that inhibits mast cell degranulation, platelet aggregation, and neutrophil function and is a potent vasodilator. The efficacy of verapamil (20 mg/kg/day) to salvage a standard failing random skin flap in the rat was studied. In this study verapamil failed to benefit skin flap survival. The results are analyzed and presented.
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PMID:Efficacy of verapamil in the salvage of failing random skin flaps. 322 3


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