Azelastine and allergen transduction signal in MC9 mast cells |
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Authors: | K Fanous R P Garay |
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Institution: | (1) INSERM U2, Faculté de Médicine, 8 rue du Général Sarrail, F-94010 Créteil, France |
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Abstract: | Summary MC9 mast cells, sensitized with monoclonal IgE antibody specific for 2,4-dinitrophenyl (DNP) group, were exposed to DNP-BSA and the pH and cytosolic calcium signals were recorded by using the fluorescent probes BCECF and Fura-2 respectively. DNP-BSA induced cell alkalinization was fully inhibited by azelastine with IC50 (1.6±0.5 mol/l, mean±SEM, n = 5) similar to that required to inhibit histamine release (1.4 mol/l), Conversely, high azelastine concentrations (> 100 mol/l) were required to inhibit DNP-BSA-dependent cell calcium mobilization (IC50 200 mol/l, n = 3). Amiloride, but not the H1 histamine antagonist pyrilamine, was able to inhibit the DNP-BSA induced pH signal. In acidified mast cells, azelastine potently inhibited Na+:H+ exchange activity (IC50 = 7.7±3.6 × 10–6 M, mean±SEM, n = 3). Conversely, in mouse spleen lymphocytes azelastine was unable to inhibit the amiloride-sensitive pH signal induced by concanavalin A. In conclusion, the inhibition of histamine release by azelastine is not due to an interference with the cytosolic calcium signal. Conversely, azelastine potently antagonized the allergen-dependent Na+: H+ exchange activation, suggesting an action on the protein kinase C signaling pathway.
Correspondence to: R. P. Garay at the above address |
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Keywords: | Azelastine Mast cells Cell membranes Calcium Histamine Na+:H+ exchanger IgE |
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