Umeki S
Department of Medicine, Kawasaki Medical School.
Arerugi. 1991 Dec;40(12):1511-20.
The effects of anti-allergic drugs with or without H1-receptor antagonism on the NADPH oxidase from human neutrophils in both whole-cell and fully soluble (cell-free) systems were investigated. Three anti-allergic drugs with H1-receptor antagonism, azelastine, ketotifen and oxatomide, were found to inhibit the superoxide generation of human neutrophils exposed to phorbol myristate acetate in a whole-cell system and the activation of superoxide-generating NADPH oxidase by sodium dodecyl sulfate in a cell-free system. The concentrations of three drugs required for 50% inhibition of the oxidase (IC50) were as follows: azelastin--0.7 microM in the whole-cell system and 0.5 microM in the cell-free system, ketotifen--60 microM in the whole-cell system and 6.8 microM in the cell-free system, and oxatomide--25 microM in the whole-cell system and 9.7 microM in the cell-free system. In addition, in the cell-free system, these drugs did not change the Km values for the NADPH of the oxidase. However, micromoles of tranilast, an anti-allergic drug without H1-receptor antagonism, did not inhibit neutrophil NADPH oxidase in the whole-cell and cell-free systems. The IC50 of hydrocortisone in the cell-free system was 60 microM. These results suggest that anti-allergic drugs with H1-receptor antagonism inhibit reconstitution of the solubilized membrane-bound enzyme by sodium dodecyl sulfate in cell-free systems and that they have a strong anti-inflammatory action. Anti-allergic drugs are not the drugs of first choice for asthma, but these drugs, especially basic anti-allergic drugs, should be used more frequently for the treatment of chronic asthma, infectious-typed asthma and mixed-typed asthma closely associated with acute and chronic inflammation of the airways as well as atopic asthma.
研究了具有或不具有H1受体拮抗作用的抗过敏药物在全细胞和完全可溶（无细胞）系统中对人中性粒细胞NADPH氧化酶的影响。发现三种具有H1受体拮抗作用的抗过敏药物，氮卓斯汀、酮替芬和奥沙米特，在全细胞系统中可抑制暴露于佛波酯肉豆蔻酸酯的人中性粒细胞的超氧化物生成，在无细胞系统中可抑制十二烷基硫酸钠对超氧化物生成NADPH氧化酶的激活。抑制氧化酶50%所需的三种药物浓度（IC50）如下：氮卓斯汀——全细胞系统中为0.7微摩尔，无细胞系统中为0.5微摩尔；酮替芬——全细胞系统中为60微摩尔，无细胞系统中为6.8微摩尔；奥沙米特——全细胞系统中为25微摩尔，无细胞系统中为9.7微摩尔。此外，在无细胞系统中，这些药物并未改变氧化酶对NADPH的Km值。然而，数微摩尔的曲尼司特，一种无H1受体拮抗作用的抗过敏药物，在全细胞和无细胞系统中均未抑制中性粒细胞NADPH氧化酶。氢化可的松在无细胞系统中的IC50为60微摩尔。这些结果表明，具有H1受体拮抗作用的抗过敏药物在无细胞系统中可抑制十二烷基硫酸钠对溶解的膜结合酶的重组，且它们具有强大的抗炎作用。抗过敏药物并非哮喘的首选药物，但这些药物，尤其是碱性抗过敏药物，应更频繁地用于治疗与气道急慢性炎症密切相关的慢性哮喘、感染型哮喘和混合型哮喘以及特应性哮喘。
