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)

We investigated the effects of terfenadine, a histamine H1-receptor antagonist, and flurbiprofen, a cyclooxygenase inhibitor, on exercise-induced bronchoconstriction to assess the contribution of the mast cell products histamine and prostaglandins. Eight asthmatics were studied on 4 occasions with treadmill exercise tests. Terfenadine or placebo was administered 3 h prior to exercise, and flurbiprofen or placebo was administered 2 h prior to exercise, in a double-blind randomized trial. Airway calibre was determined by measurement of the forced expiratory volume in one second (FEV1) immediately prior to exercise challenge, and over 30 min post-exercise. Following placebo, the mean maximum percentage fall in FEV1 was 39%. This fell to 25% after terfenadine (p less than 0.05), 27% after flurbiprofen (p less than 0.05), and 30% after the active combination (NS). Analysis of the areas under curves of percentage falls in FEV1 over 30 min showed significant inhibition on all 3 active drug days (p less than 0.05). We conclude that histamine release and prostaglandin generation contribute to exercise-induced bronchoconstriction, although the interaction between these mediators appears complex.
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PMID:Evidence for the roles of histamine and prostaglandins as mediators in exercise-induced asthma: the inhibitory effect of terfenadine and flurbiprofen alone and in combination. 169 77

We have investigated the role of histamine in allergen and adenosine-5'-monophosphate (AMP)-induced bronchoconstriction in asthmatic subjects by performing inhalation challenge tests with histamine, AMP and allergen after treatment with placebo or the potent H1 histamine receptor antagonist, terfenadine. Single concentrations of each agonist which had previously been shown to produce a 30% fall in FEV1 were used. After placebo, AMP and histamine both produced rapid bronchoconstriction reaching a maximum within 5 min and returning to within 10% of baseline after 25 min. Terfenadine inhibited this reaction to histamine completely and to AMP by 86%. The response to allergen was slower in onset and was sustained over 45 min and was inhibited 50% by terfenadine. We interpret these results as reflecting the contribution of histamine to the various airway challenges, both histamine and newly generated mediators comprise the response to allergen, whereas AMP selectively enhances mast cell degranulation without affecting the production of arachidonic acid derived mediators.
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PMID:The role of histamine in allergen and adenosine-induced bronchoconstriction. 288 29

H1-blockers may have antiallergic properties which cause the blocking of eicosanoid release, and the effect of these drugs may differ according to the phenotype of mast cells. This study examined the ability of terfenadine and cetirizine to inhibit the release of arachidonic acid-derived mediators from human lung and colon cells. Dispersed cells were challenged with anti-IgE in the presence or absence of 10 microM of terfenadine or cetirizine, and the release of prostaglandin (PG)D2 and leukotriene (LT)C4/D4 was assessed by enzyme immunoassay (EIA). Terfenadine caused significant inhibition of both PGD2 and LTC4/D4 (49 +/- 9 and 29 +/- 19%, respectively) from human lung cells but had a less marked effect on PGD2 release from human colon cells (21 +/- 9% for PGD2 and 18 +/- 9% for LTC4/D4). In contrast, although cetirizine caused significant inhibition of both mediators measured in lung cells (38 +/- 16% for PGD2 and 34 +/- 19% for LTC4), it did not cause any significant inhibition of either mediator from human colon cells. These findings suggest that H1-antagonists may have additional properties, and the differential effects of cetirizine on lung and colon tissue may indicate differences in mast cell phenotype.
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PMID:Pharmacologic heterogeneity of human lung and colon cells: effect of terfenadine and cetirizine. 757 21

We are interested in understanding the pathogenesis of the cutaneous IgE-mediated late phase reaction. A double-blind, placebo-controlled, randomized cross-over study with 10 subjects of the effect of the non-sedating antihistamine, terfenadine (Selddane), on the cutaneous reaction to antigen (ragweed or mixed grass) administered intradermally and over denuded blister bases was performed. The activity of terfenadine on anti-IgE-induced mediator release from the skin mast cell, lung mast cell and basophil was also examined in vitro. Terfenadine significantly inhibited the size of the cutaneous reaction at every hour between hours 1 and 9 (hr 9, control 2250 +/- 500 mm2 vs drug 1250 +/- 250 mm2, P < 0.01, n = 10) and showed some inhibitory effect at hours 10-12. While terfenadine blocks histamine release after nasal antigen challenge the release of mediators at skin blister sites was unaffected. The infiltration of leucocytes into the blister supernatant was unaffected by terfenadine although previous studies have shown significant inhibition with another antihistamine, cetirizine. In vitro, terfenadine, like other antihistamines, was found to have inhibitory activity on anti-IgE-induced mediator release at concentrations of 10(-4)-10(-5) M in lung and skin mast cells and basophils. We conclude that the effects of the newer antihistamines on cellular movement into the skin may be diverse, that terfenadine may show organ specificity in vivo and that terfenadine significantly decreases both the early and late gross inflammatory response of the skin to antigen. We cannot, as yet, explain the mechanism(s) by which this occurs.
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PMID:Cutaneous IgE-mediated inflammatory lesion size is inhibited by an H1 antagonist (terfenadine) while mediator release is unaffected in vivo and in vitro. 768 10

Antihistamines are believed to reduce the sneezing and rhinorrhea associated with allergic rhinitis, primarily by competitive antagonism of histamine for H1 cellular receptors, but additional mechanisms of action may contribute to their clinical efficacy. To improve our understanding of H1 antihistamine action, we studied the effects of pretreatment with terfenadine, cetirizine, ketotifen, azatadine, diphenhydramine, and azelastine on increases in vascular permeability, mast cell activation, and sneezing induced by nasal challenge with antigen. All studied antihistamines reduced sneezing, indicating that they all effectively antagonize histamine after its release. In addition, terfenadine and topically administered azatadine blocked the release of histamine. Studies with cetirizine and azelastine revealed that these antihistamines significantly reduced sulfidopeptide leukotriene levels. Terfenadine and azelastine also reduced kinin production. These results confirm that antihistamines are effective in reducing sneezing and, in some cases, vascular permeability. The findings of these studies also illustrate that the various antihistamines have multiple and different mechanisms of action that may have implications for their clinical uses.
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PMID:The effect of antihistamines on the immediate allergic response: a comparative review. 810 58

Female NC/Jic mice were sensitized and challenged repeatedly at 48 h intervals for 10 and 30 days by painting 1% 2,4,6-trinitrochlorobenzene (TNCB) on both ears. Mice challenged with TNCB for 30 days developed an inflammatory dermatitis with high immunoglobulin E (IgE) titer. Histological analysis with acidic Toluidine Blue staining revealed that dermal mast cells markedly differentiated and intensely degranulated, consistent with a dramatic increase in scratching behavior. A significant increase in total scratching events could be observed in mice treated with TNCB for a short period of 10 days. Extending the term of TNCB application to 30 days, the IgE titer and number of mast cells elevated significantly, and thus various drugs were evaluated pharmacologically by using the mice treated with TNCB for 30 days. Terfenadine and cyproheptadine attenuated the chronic scratching behavior. Tacrolimus and dexamethasone were less effective and cromolyn showed no effect. In addition, terfenadine and tacrolimus suppressed the degranulation of mast cells. The present chronic scratching model could be suitable to evaluate drugs effective for suppression of mast cell differentiation and degranulation by irritation, and may represent a promising tool to develop new drugs for inflammatory pruritus associated with, for example, atopic dermatitis.
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PMID:Pharmacological characterization of a chronic pruritus model induced by multiple application of 2,4,6-trinitrochlorobenzene in NC mice. 1733 91