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)

Allergic rhinitis is a classic example of a type I immunological reaction. After allergic provocation tests a biphasic reaction is seen in the respiratory tract that is more pronounced in the lower than in the upper respiratory tract due to the physiological changes during the nasal cycle. The early phase of the immediate reaction starts some minutes after allergen provocation. After 5-10 h the nasal symptoms (discharge, blockage, sneezing and itching of the nose) reappear, a phenomenon which is called the "late-phase response" (LPR). The LPR is of great clinical importance in the pathophysiology of perennial allergic rhinitis and phenomena such as nasal priming and nasal hyper-reactivity. The most important effector cell of the early phase of the immediate reaction is the mast cell, whereas basophils, eosinophils and neutrophil granulocytes seem to be more important for the LPR. There is also evidence for morphological and functional heterogeneity of mast cells in man. The role of the chemotactically immigrated eosinophils in allergic reactions has not been clear until now: the eosinophil-derived mediators may enhance or inhibit the allergic reaction. Also the eosinophils show different morphological and functional states (so-called hypo- and hyperdense eosinophils). The symptoms of allergic rhinitis (sneezing, discharge, blockage, itching of the nose) are caused by different mediators, of which the most important is histamine. Other mediators or modulators of the allergic reactions are leucotrienes, prostaglandins, PAF, serotonin, and the kallikrein-kinine and complement systems. In recent years many regulatory peptides have been detected in the human nasal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Current pathophysiologic aspects of allergic rhinitis. I]. 226 46

A nasal challenge model of allergic rhinitis was used to determine if pretreatment with oral theophylline reduces histamine release in vivo. Ten subjects were entered into a double-blind, cross-over trial. The results showed that both the physiologic response (sneezing) (p = 0.02) and the amount of mediators (histamine, kinins, toluene sulfonyl arginine methyl ester esterase activity) (p less than 0.01 for all) released into nasal secretions were significantly reduced after one week of pretreatment with theophylline. At the time of challenge, the serum concentrations of theophylline were between 8 and 22 micrograms/ml. It is speculated that the ability of theophylline to block the clinical response to antigen challenge and to decrease the release of mast cell mediators contributes to its clinical efficacy in the treatment of asthma.
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PMID:Theophylline reduces the response to nasal challenge with antigen. 241 77

A double blind, placebo-controlled, cross-over study was performed to determine the effect of cetirizine, an H1 antihistamine, on the immediate nasal allergic response. Ten persons underwent nasal challenge with antigen after premedication with 20 mg of cetirizine or placebo QD for 2 days. The response was monitored by counting the number of sneezes and by measuring the levels of histamine, prostaglandin D2, leukotriene C4, albumin, and TAME-esterase activity in recovered nasal lavages. The results showed a significant reduction in sneezing and in the amounts of recovered albumin, TAME-esterase activity, and leukotriene C4 but no reduction in the amounts of recovered histamine and prostaglandin D2. These results suggest that cetirizine does not inhibit mast cell activation but inhibits the consequences of the released histamine on H1 receptors: sneezing and increased vascular permeability. The results further suggest that mast cell release of histamine is the direct result of antigen stimulation, as opposed to reflex activation, and that other cells in addition to mast cells generate leukotrienes during the early allergic response.
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PMID:The effect of cetirizine on early allergic response. 256 79

A nasal antigen challenge model of allergic individuals was used to evaluate whether antihistamines could inhibit human mast cell and basophil mediator release in vivo. In placebo-controlled trials, topically applied azatadine base, a tricyclic antihistamine with in vitro antirelease action, effectively reduced symptoms and mediator levels in nasal lavage fluids after antigen challenge, suggesting mast cell inhibition. Both terfenadine and cetirizine, systemically administered antihistamines, were clinically effective in reducing sneezing and changes in vascular permeability. Only terfenadine significantly reduced histamine in antigen-induced nasal secretions. However, cetirizine did reduce the level of leukotriene C4 in these fluids. These results indicate that some antihistamines may be capable of suppressing mediator release from nasal mast cells. The significance of this property in those compounds' overall clinical effect is unclear because of their other concomitant activities.
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PMID:In vivo and in vitro effects of antihistamines on mast cell mediator release: a potentially important property in the treatment of allergic disease. 257 1

To increase understanding of the effect of H1 antihistamines on the immediate response to nasal challenge with antigen, we performed two double blind, placebo-controlled, crossover studies using cetirizine and terfenadine. The subjects underwent nasal challenge with antigen after premedication with either cetirizine (20 mg QD for two days, n = 10), terfenadine (60 mg BID for 1 week, n = 12), or placebo for equivalent periods of time. We monitored the response to challenge by counting the number of sneezes and by measuring the levels of inflammatory substances in recovered nasal lavages. Compared with placebo, both antihistamines significantly reduced sneezing and the levels of recovered albumin and TAME esterase activity, suggesting that both reduced the expected increase in vascular permeability. With cetirizine, there was also a reduction in the levels of LTC4 (not measured in terfenadine studies) but not in those of recovered histamine and prostaglandin D2. These data suggest that cetirizine did not affect mast cell mediator release, that histamine release is due to the direct action of antigen stimulation and that leukotrienes are generated by cells in addition to mast cells. With terfenadine, there were significant reductions in the levels of histamine and kinins (not measured in cetirizine study) seen after nasal challenge with antigen. The reduction in kinins most likely reflects alteration in vascular permeability, whereas the effect on histamine presumably reflects inhibition of mast cell activation. When combined, these experiments demonstrate effects of H1 antihistamines on histamine release beyond those usually described, as well as differences between drugs within a single classification.
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PMID:The effects of H1 antihistamines on the early allergic response. 257 50

The clinical manifestations of allergic rhinitis are the result of an immune-mediated process after exposure of a sensitized individual to airborne allergens. The primary symptomatology includes nasal congestion, rhinorrhea, nasal and conjunctival pruritus, and sneezing. Principles of management include allergen avoidance, palliative therapy, immunotherapy, and pharmacotherapy. Oral decongestants stimulate alpha-adrenergic receptors in the nasal cavity, resulting in vasoconstriction and decreased edema. Oral antihistamines block histamine1 (H1) receptors, and may relieve rhinorrhea, sneezing, and nasal and conjunctival pruritus. Topical decongestants have a local effect on adrenergic receptors in the nasal mucosa, resulting in rapid, marked vasoconstriction. Intranasal corticosteroids inhibit mediator release from mast cells and basophils, and reduce edema of the nasal mucosa. Dexamethasone sodium phosphate, beclomethasone dipropionate, and flunisolide are currently available for intranasal administration. Cromolyn sodium inhibits allergen-induced degranulation and mediator release from sensitized cells, and is useful primarily as a prophylactic agent. Several agents, including the corticosteroids budesonide and flucortin butylester, the mast cell-stabilizing agent nedocromil sodium, the anticholinergic agent ipratropium bromide, and the H1 receptor antagonist levocabastine are being investigated for intranasal use in the management of allergic rhinitis.
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PMID:Management of allergic rhinitis: focus on intranasal agents. 257 39

Research in molecular biology in the past few years offers new views on vasomotor rhinitis. The key role of mediator substances which contain the mast cell and which, after degranulation, are active immediately by histamine release or act in a delayed manner (eg. leucotriene), is discussed, as well as the "liberofunction" of the neurotransmitter acetylcholine. The contribution to vasomotor rhinitis of other humoral systems, the kinine system and complement factors are also taken into account. The biopharmacological actions of the effector systems of the nasal mucosa (vessels, exocrine glands, nociceptors) are also analyzed. Using clinical examples the differentiation between humoral or neural reflex mediated hyperreflexia is worked out related to the classic triad of sneezing, profuse nasal discharge, nasal obstruction. The causes of vasomotor rhinitis (exogenous endogenous and drugs) are examined in the light of their pathophysiological importance. The differential diagnosis must cover allergic rhinopathy as well as the different kinds of rhinitis medicamentosa, the most important of which are discussed. Drugs which can help are discussed as well as continuous physical therapy.
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PMID:[Hyperreflectoric rhinopathy]. 257 36

To examine mast cell involvement in allergic rhinitis, levels of tryptase, a specific marker for mast cell activation, and histamine, a marker of mast cell and basophil activation, were measured in nasal-lavage fluid after nasal-allergen challenge. Twelve atopic subjects with allergic rhinitis and five nonatopic subjects were challenged with timothy grass or ragweed pollen at increasing doses of allergen. Tryptase and histamine levels were determined by an ELISA and radioenzyme assay, respectively; clinical responses were measured by assessment of sneezing, rhinorrhea, nasal congestion, and ocular tearing or itching. A positive clinical response was observed in seven of the atopic subjects and in none of the nonatopic subjects. Tryptase levels increased at least sevenfold higher than baseline levels in 100% of the atopic clinical responders and reached a maximum at the same dose of allergen where clinical symptoms were maximal. In contrast, histamine levels were only threefold or greater elevated in five of seven atopic clinical responders at this dose of allergen. (Histamine levels were lower in one subject and were only 50% higher in another subject than the corresponding baseline value.) Histamine levels and symptom scores were maximal at the same dose of allergen in only four of seven clinical responders. Overlap of peak mediator levels in subjects without a clinical response with those of the clinical responders occurred only in the case of histamine. Tryptase levels in nasal-lavage fluid appear promising as a useful indicator of allergic reactions and indicate that mast cell activation is the major factor in the immediate nasal-allergic response.
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PMID:Tryptase levels in nasal-lavage fluid as an indicator of the immediate allergic response. 304 43

In order to assess the role of arachidonic acid metabolites in the early reaction to antigen, we challenged six allergic individuals with and without premedication with aspirin and recorded their clinical response, as indicated by number of sneezes, and measured the levels of inflammatory mediators. The early reaction to antigen was associated with increases in the levels of histamine, N-alpha-tosyl-L-arginine methyl esterase (TAME-esterase) activity, prostaglandin (PG) D2, leukotriene C4, PGE, and thromboxane. Aspirin significantly inhibited the increases in the cyclooxygenase metabolites PGE, PGD2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane but did not affect the amount of sneezing or the levels of histamine, TAME-esterase activity, or leukotrienes. The pattern of the metabolites and their response to pretreatment with aspirin parallel the response of purified human lung mast cells, supporting the notion that the early phase of allergic rhinitis is a mast cell-dominated event.
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PMID:Arachidonic acid metabolites during nasal challenge. 309 12

A novel human in vivo model of intranasal challenge with antigen is used to demonstrate the effectiveness of a topical antirelease drug. Previous experimentation has established a highly significant correlation between the physiologic response of sneezing, which occurs after insufflation of antigen into the nose of allergic individuals, and the recovery of putative mast cell mediators: histamine, tosyl arginine methyl ester (TAME)-esterase(s), and prostaglandin D2- Azatadine base, a tricyclic antihistamine, which also inhibits mediator release in vitro, applied prior to antigen administration not only reduces the clinical symptom of sneezing but simultaneously reduces the concentration of the inflammatory mediator, TAME-esterase(s), recovered from nasal washes. To our knowledge, this is the first observation that an antirelease drug can stop mediator release in vivo in the nose.
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PMID:In vivo model for the evaluation of topical antiallergic medications. 613 98


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