Effect of azelastine on the release and action of leukotriene C4 and D4.
Effect of azelastine on the release and action of leukotriene C4 and D4.
复制标题
氮卓斯汀对白三烯 C4 和 D4 的释放和作用的影响。
DOI：
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发表时间：
1987
期刊：
影响因子：
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通讯作者：
K. Katayama
中科院分区：
文献类型：
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作者：
S. Katayama;H. Tsunoda;Y. Sakuma;H. Kai;I. Tanaka;K. Katayama
通过体外试验测定氮卓斯汀对白三烯C4和D4（LTC4和LTD4）释放的影响以及药物对白三烯的拮抗作用，并与酮替芬和扑尔敏进行比较。氮斯汀抑制LTC4和LTD4从用同源抗卵清蛋白IgG1-b抗体被动致敏的豚鼠肺片段中释放。氮卓斯汀的 50% 抑制浓度 (IC50) 为 6.4 X 10(-5) M（预孵育 15 分钟）或 4.7 X 10(-5) M（预孵育 30 分钟）。酮替芬和扑尔敏仅在最高测试浓度（3 X 10(-4) M）下具有抑制作用，抑制率分别为 35.6% 和 21.3%。 Azelastine 还可以抑制钙离子载体 A23187 诱导的人多形核白细胞释放白三烯。预孵育15分钟的IC50值为3.6 X 10(-5) M，预孵育30分钟的IC50值为2.3 X 10(-6) M。酮替芬和扑尔敏仅在预孵育30分钟后才具有抑制作用，IC50值分别为2.1 X 10(-5) 和5.9 X 10(-5) M。氮卓斯汀的有效抑制作用可能部分是由于抑制 5-脂氧合酶，因为氮卓斯汀抑制大鼠嗜碱性白血病细胞匀浆中 5-羟基二十碳四烯酸的形成。用氮斯汀预处理豚鼠回肠可拮抗 LTC4 和 LTD4 诱导的回肠收缩，IC50 值分别为 7.0 X 10(-6) 和 1.1 X 10(-5) M。（摘要截断为 250 字）
The effect of azelastine on the release of leukotriene C4 and D4 (LTC4 and LTD4), and the antagonistic action of the drug against the leukotrienes were determined by using in vitro tests and compared with those of ketotifen and chlorpheniramine. Azelastine inhibited LTC4 and LTD4 release from guinea pig lung fragments passively sensitized with homologous anti-ovalbumin IgGl-b antibody. The 50% inhibitory concentration (IC50) of azelastine was 6.4 X 10(-5) M for a 15-min preincubation or 4.7 X 10(-5) M for a 30-min preincubation. Ketotifen and chlorpheniramine were inhibitory only at the highest concentration tested (3 X 10(-4) M), giving inhibitions of 35.6 and 21.3%, respectively. Azelastine also inhibited calcium ionophore A23187-induced release of leukotrienes from human polymorphonuclear leukocytes; the IC50 values were 3.6 X 10(-5) M for 15 min and 2.3 X 10(-6) M for 30 min of preincubation. Ketotifen and chlorpheniramine were inhibitory only after a 30-min preincubation, with IC50 values of 2.1 X 10(-5) and 5.9 X 10(-5) M, respectively. The potent inhibition by azelastine might be partly a result of the inhibition of 5-lipoxygenase, since 5-hydroxyeicosatetraenoic acid formation in rat basophilic leukemia cell homogenate was inhibited by azelastine. Pretreatment of guinea pig ileum with azelastine antagonized LTC4- and LTD4-induced contraction of the ileum with IC50 values of 7.0 X 10(-6) and 1.1 X 10(-5) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)