Effect of cetirizine on antigen-induced tracheal contraction of passively sensitized guinea pigs

Background: Cetirizine dihydrochloride (cetirizine), a potent histamine H-1-receptor antagonist, has been developed as an anti-allergy drug. Object: The anti-allergic effects and mechanism of cetirizine were studied using in vitro assay systems. Methods: We investigated the effect of cetirizine on antigen-induced contractions of isolated tracheal strips and on chemical mediator release from antigen-stimulated lung chips taken from passively sensitized guinea pigs. We examined the antigen-induced mobilization of Ca2+ in MC/9 mast cells sensitized with IgE. Results: Cetirizine inhibited the antigen-induced contraction of isolated guineapig trachea concentration dependently. Pyrilamine, another histamine H-1-receptor antagonist, delayed the response but did not change the maximum amplitude. Cetirizine at the concentration of 3 mu M also inhibited the antigen-induced release of histamine, leukotriene D4, and leukotriene E4 from guinea pig lung chips. Furthermore, it inhibited the antigen-induced Ca2+ increase in MC/9 mast cells, whereas pyrilamine did not. Conclusion: These findings suggest that one anti-allergic mechanism of cetirizine may inhibit mediator release which is, at least partially, mediated by a decrease in the transient Ca2+ influx in mast cells.