Effect of cetirizine on antigen-induced tracheal contraction of passively sensitized guinea pigs.
BACKGROUND
Cetirizine dihydrochloride (cetirizine), a potent histamine H1-receptor antagonist, has been developed as an anti-allergy drug.


OBJECTIVE
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 guinea-pig trachea concentration dependently. Pyrilamine, another histamine H1-receptor antagonist, delayed the response but did not change the maximum amplitude. Cetirizine at the concentration of 3 microM 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.


CONCLUSIONS
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.
Dobashi
K
K
First Department of Internal Medicine, Gunma University, School of Medicine, Japan.
Iizuka
K
K
Houjou
S
S
Sakai
H
H
Watanabe
K
K
Mori
M
M
Nakazawa
T
T
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000941:Antigens; D002118:Calcium / Q000032:analysis; D002478:Cells, Cultured; D017332:Cetirizine / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000276:immunology / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006636:Histamine Release; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects; D011738:Pyrilamine / Q000494:pharmacology; D014132:Trachea / Q000502:physiology*
D018926:Anti-Allergic Agents; D000941:Antigens; D006634:Histamine H1 Antagonists; D006632:Histamine; D011738:Pyrilamine; D002118:Calcium; D017332:Cetirizine