Burka J F
Br J Pharmacol. 1985 Jun;85(2):411-20. doi: 10.1111/j.1476-5381.1985.tb08876.x.
Ovalbumin (OA) and calcium ionophore A23187 were used to induce contractions of sensitized guinea-pig tracheal and lung parenchymal preparations in the presence and absence of indomethacin. This model was used to examine the properties of a series of compounds reported to inhibit 5-lipoxygenase or to antagonize lipoxygenase products at the receptor level. FPL55712 and piriprost appeared to act as pharmacological antagonists because they rapidly reduced tracheal tone established by OA. The prolonged phase (i.e. greater than 10 min post-challenge) of airways contractions induced by OA is assumed to be lipoxygenase-dependent and was inhibited by nordihydroguaiaretic acid (NDGA), FPL55712, nafazatrom and benoxaprofen, in order of potency. Piriprost had similar inhibitory effects on the trachea, but not on lung parenchyma. The inhibitory effects of NDGA and FPL55712 were reduced, and those of nafazatrom increased by indomethacin. Indomethacin decreased the inhibitory effect of piriprost on the trachea, but facilitated inhibition by this agent on the parenchyma. A roughly similar pattern was seen on A23187-induced contractions, but FPL55712 did not modify these contractions and benoxaprofen enhanced the response of the trachea. BW755C enhanced the overall contractile response of OA- and A23187-induced tracheal contractions (but not parenchymal contractions) in a bell-shaped manner, an effect not seen in the presence of indomethacin. This indicated that BW755C could be acting as a cyclo-oxygenase inhibitor. The results suggested that, although inhibitors of the lipoxygenase pathway were partially effective in inhibiting the contractions of the airways induced by OA or A23187, other mediators in addition to those of the lipoxygenase pathway contribute to these contractions.
在存在和不存在消炎痛的情况下，使用卵清蛋白（OA）和钙离子载体A23187诱导致敏豚鼠气管和肺实质制剂收缩。该模型用于研究一系列据报道可抑制5-脂氧合酶或在受体水平拮抗脂氧合酶产物的化合物的特性。FPL55712和吡嘧司特似乎作为药理拮抗剂起作用，因为它们能迅速降低由OA建立的气管张力。OA诱导的气道收缩的延长阶段（即激发后大于10分钟）被认为是脂氧合酶依赖性的，并被去甲二氢愈创木酸（NDGA）、FPL55712、萘呋胺酯和苯恶洛芬按效力顺序抑制。吡嘧司特对气管有类似的抑制作用，但对肺实质无作用。消炎痛可降低NDGA和FPL55712的抑制作用，增加萘呋胺酯的抑制作用。消炎痛降低了吡嘧司特对气管的抑制作用，但促进了该药物对实质的抑制作用。在A23187诱导的收缩中观察到大致相似的模式，但FPL55712不改变这些收缩，苯恶洛芬增强了气管的反应。BW755C以钟形方式增强了OA和A23187诱导的气管收缩（但不增强实质收缩）的总体收缩反应，在存在消炎痛的情况下未观察到这种效应。这表明BW755C可能作为环氧化酶抑制剂起作用。结果表明，尽管脂氧合酶途径抑制剂在抑制OA或A23187诱导的气道收缩方面部分有效，但除脂氧合酶途径的介质外，其他介质也参与了这些收缩。
