Action of azelastine on intracellular Ca2+ in cultured airway smooth muscle.
Azelastine, a novel antiasthmatic/antiallergic agent, was tested for Ca2+ 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 IC50 value of 1.1 +/- 0.3 x 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 IC50 value of 6.7 +/- 2.9 x 10(-5) M. Moreover, azelastine fully blocked histamine-induced calcium mobilization (IC50 = 7 x 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.
Senn
N
N
Inserm, Hôpital Necker, Paris, France.
Jeanclos
E
E
Garay
R
R
D000818:Animals; D001127:Arginine Vasopressin / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D010793:Phthalazines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D006634:Histamine H1 Antagonists; D010793:Phthalazines; D001127:Arginine Vasopressin; D002118:Calcium; C020976:azelastine