Garceau D, Ford-Hutchinson A W, Charleson S
Department of Pharmacology, Merck Frosst Canada Inc., Pointe Claire-Dorval, Québec, Canada.
Eur J Pharmacol. 1987 Nov 3;143(1):1-7. doi: 10.1016/0014-2999(87)90728-x.
The role of leukotrienes as mediators of microvascular permeability changes (assessed through the accumulation of [99mTc]albumin) associated with immediate hypersensitivity reactions in the guinea-pig conjunctiva was investigated by means of two novel, structurally dissimilar 5-lipoxygenase inhibitors, L-651,392 and L-651,896. Both compounds, when applied topically in vivo to the eyes of sensitized guinea-pigs as a 0.1% suspension significantly inhibited 5-lipoxygenase in the conjunctiva as assessed by ex vivo challenge with either antigen or ionophore A23187 and measurement of the release of leukotriene B4-immunoreactive material. Topical application of antigen (either single challenge or 2 challenges separated by 24 h) to the eyes of sensitized guinea-pigs produced changes in conjunctival permeability which were blocked in part by either mepyramine (H1-receptor antagonist) or the 5-lipoxygenase inhibitors. Combinations of mepyramine and L-651,896 resulted in near complete suppression of the permeability response, suggesting that the reaction is mediated only by histamine and leukotrienes.
通过两种新型的、结构不同的5-脂氧合酶抑制剂L-651,392和L-651,896，研究了白三烯在豚鼠结膜中与速发型超敏反应相关的微血管通透性变化（通过[99mTc]白蛋白的积聚来评估）中的介导作用。当以0.1%悬浮液局部应用于致敏豚鼠的眼睛时，通过用抗原或离子载体A23187进行离体激发并测量白三烯B4免疫反应性物质的释放来评估，这两种化合物均能显著抑制结膜中的5-脂氧合酶。将抗原局部应用于致敏豚鼠的眼睛（单次激发或间隔24小时进行两次激发）会引起结膜通透性的变化，而这种变化部分被美吡拉敏（H1受体拮抗剂）或5-脂氧合酶抑制剂所阻断。美吡拉敏和L-651,896的组合几乎完全抑制了通透性反应，表明该反应仅由组胺和白三烯介导。
