Dobashi K, Iizuka K, Houjou S, Sakai H, Watanabe K, Mori M, Nakazawa T
First Department of Internal Medicine, Gunma University, School of Medicine, Japan.
Ann Allergy Asthma Immunol. 1996 Oct;77(4):310-8. doi: 10.1016/S1081-1206(10)63326-1.
Cetirizine dihydrochloride (cetirizine), a potent histamine H1-receptor antagonist, has been developed as an anti-allergy drug.
The anti-allergic effects and mechanism of cetirizine were studied using in vitro assay systems.
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.
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.
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.
盐酸西替利嗪（西替利嗪）是一种强效组胺H1受体拮抗剂，已被开发为一种抗过敏药物。
使用体外测定系统研究西替利嗪的抗过敏作用及其机制。
我们研究了西替利嗪对离体气管条抗原诱导的收缩作用以及对来自被动致敏豚鼠的抗原刺激肺片化学介质释放的影响。我们检测了IgE致敏的MC/9肥大细胞中抗原诱导的Ca2+动员情况。
西替利嗪浓度依赖性地抑制离体豚鼠气管的抗原诱导收缩。另一种组胺H1受体拮抗剂吡苄明延迟了反应，但未改变最大振幅。3 microM浓度的西替利嗪也抑制了豚鼠肺片抗原诱导的组胺、白三烯D4和白三烯E4释放。此外，它抑制了抗原诱导的MC/9肥大细胞中Ca2+增加，而吡苄明则没有。
这些发现表明，西替利嗪的一种抗过敏机制可能是抑制介质释放，这至少部分是由肥大细胞中瞬时Ca2+内流减少介导的。
