Action of azelastine on intracellular Ca 2+ in cultured airway smooth muscle

Abstract

Azelastine, a novel antiasthmatic/ antiallergic agent, was tested for Ca 2+ antagonistic properties in cultured rabbit airway smooth muscle, vascular smooth muscle and cardiocytes. In airway smooth muscle cells, the basal cytosolic free calcium content was 195 ± 72 nM (mean ± S.D., n = 18). These basal values were decreased by azelastine with an IC 50 value of 1.1 ± 0.3 × 10 −4 M. Endothelin-1 (10 −7 M) induced a rapid increase in free cytosolic calcium up to 806 ± 314 nM, which returned to normal levels in 3–5 min. This was fully blocked by azelastine in a concentration-dependent manner, with an IC 50 value of 6.7 ± 2.9 X 10 −5 M. Moreover, azelastine fully blocked histamine-induced calcium mobilization (IC 50 = 7 × 10 −5 M). In cultured vascular smooth muscle cells and cardiocytes, azelastine was unable to decrease the basal cytosolic free calcium content or inhibit agonist-induced calcium mobilization. Therefore, at therapeutic levels, a specific, mild inhibition of calcium mobilization in airway smooth muscle may be one component of the antiasthmatic action of azelastine.