Antiallergic effects of astemizole on immediate type hypersensitivity reactions.
Antiallergic effects of astemizole on immediate type hypersensitivity reactions.
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阿司咪唑对速发型超敏反应的抗过敏作用。
DOI：
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发表时间：
1990
影响因子：
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通讯作者：
M. Mio
中科院分区：
文献类型：
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作者：
K. Tasaka;M. Akagi;K. Izushi;M. Mio
阿司咪唑(0.5-5 mg/kg，P.O.)ID50分别为1.48 mg/kg和2.37 mg/kg时，均呈剂量依赖性抑制大鼠异种和同种PCA反应。口服阿司咪唑对异种前列腺癌的抑制作用最为显著。抗原攻击前2小时。阿司咪唑(0.1-5 mg/kg，P.O.)对豚鼠实验性哮喘有剂量依赖性抑制作用，ID50为0.86 mg/kg。阿司咪唑(0.5-5 mg/kg，P.O.)抑制致敏豚鼠肺片抗原诱导的组胺释放。在体外实验中，该药物在0.05-10微米的浓度下呈剂量依赖性地抑制抗原诱导的豚鼠肺片的组胺和SRS-A的释放。此外，阿司咪唑(0.1-10微米)抑制化合物48/80诱导的组胺释放和大鼠腹膜肥大细胞的抗原抗体反应，在0.1-500 nM时抑制白三烯C4和血小板活化因子(PAF)诱导的豚鼠离体气管收缩。阿司咪唑不仅能抑制大鼠肥大细胞摄取~(45)Ca，而且能抑制化合物48/80诱导的细胞内钙离子释放，但不影响钙离子诱导的通透性肥大细胞释放组胺。我们的结果提示阿司咪唑的抗过敏机制之一可能是抑制肥大细胞膜到细胞内系统的信号转导。
Astemizole (0.5-5 mg/kg, p.o.) dose-dependently inhibited heterologous and homologous PCA reactions in rats at ID50 values of 1.48 mg/kg and 2.37 mg/kg, respectively. The inhibitory effect of astemizole on heterologous PCA was most remarkable when this compound was given p.o. 2 h prior to antigen challenge. Astemizole (0.1-5 mg/kg, p.o.) dose-dependently inhibited experimentally-induced asthma in guinea pigs at an ID50 of 0.86 mg/kg. Ex vivo, astemizole (0.5-5 mg/kg, p.o.) inhibited antigen-induced histamine release from lung pieces of sensitized guinea pigs. In in vitro experiments, the drug dose-dependently inhibited antigen-induced histamine and SRS-A releases from guinea pig lung pieces at concentrations of 0.05-10 microM. Furthermore, astemizole (0.1-10 microM) inhibited the histamine release induced by compound 48/80 and antigen-antibody reaction from rat peritoneal mast cells, and at 0.1-500 nM inhibited both leukotriene C4- and platelet-activating factor (PAF)-induced contraction of isolated guinea pig trachea at submicromolar concentrations. Astemizole not only inhibited 45Ca uptake into rat mast cells but also prevented the Ca2+ release from the intracellular Ca store induced by compound 48/80, although this compound did not affect the histamine release from permeabilized mast cells induced by Ca2+. Our results suggest that one of the antiallergic mechanisms of astemizole may be an inhibition of signal transduction from the mast cell membrane to the intracellular systems.