Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 348, Issue 5, pp 515–519

Azelastine and allergen transduction signal in MC9 mast cells

  • K. Fanous
  • R. P. Garay
Original Articles

DOI: 10.1007/BF00173212

Cite this article as:
Fanous, K. & Garay, R.P. Naunyn-Schmiedeberg's Arch Pharmacol (1993) 348: 515. doi:10.1007/BF00173212


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 μmol/l, mean±SEM, n = 5) similar to that required to inhibit histamine release (1.4 μmol/l), Conversely, high azelastine concentrations (> 100 μmol/l) were required to inhibit DNP-BSA-dependent cell calcium mobilization (IC50≈200 μmol/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.

Key words

AzelastineMast cellsCell membranesCalciumHistamineNa+:H+ exchangerIgE

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • K. Fanous
    • 1
  • R. P. Garay
    • 1
  1. 1.INSERM U2Faculté de MédicineCréteilFrance