Influence of epithelial removal on the antihistaminic activity of azelastine in the guinea-pig airway smooth muscles.

The influence of epithelial removal on the antihistaminic activity of azelastine in the guinea-pig isolated cervical trachea and main bronchus was examined. In both preparations with an intact epithelium, histamine produced a concentration-dependent contraction, but its potency (pD2) and contractility (Emax) were significantly higher in the main bronchus than in the cervical trachea. Epithelial removal from these preparations significantly increased the pD2 values in both tracheal and bronchial preparation, while the Emax value was significantly increased only in the cervical trachea. When these preparations were pretreated with azelastine (20 or 200 nM), concentration-response curves for histamine shifted downward, but were not influenced by the presence of an intact epithelium. Neither concentration of azelastine significantly modified the contractile responsiveness of tracheal and bronchial preparations to carbachol or neurokinin A. These results indicate that azelastine selectively antagonizes the histamine-induced contraction of the guinea-pig airway smooth muscles with or without an intact epithelium.