Inhibition of the release of slow‐reacting substance of anaphylaxis by inhibitors of lipoxygenase activity
Inhibition of the release of slow‐reacting substance of anaphylaxis by inhibitors of lipoxygenase activity
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脂氧合酶活性抑制剂抑制过敏反应慢反应物质的释放
DOI：
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发表时间：
1980
期刊：
影响因子：
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通讯作者：
W. Dawson
中科院分区：
文献类型：
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作者：
J. Walker;J. Boot;B. Cox;W. Dawson
最近的证据表明，5-羟基-6-谷胱甘肽-二十碳四烯酸（白三烯C）及其可能的降解产物5-羟基-6-半胱氨酰甘氨酸二十碳四烯酸（白三烯D）均有助于迄今为止被称为过敏反应慢反应物质（SRS-A）的生物活性（Orning et al 1980; Morris et al 1980 b）。这些化合物被认为源自5-过氧化氢-二十碳四烯酸（5-HPETE），该5-HPETE是由脂肪氧合酶氧化花生四烯酸产生的（Samuelsson等人，1979）。脂氧合酶活性在SRS-A生产中起关键作用的可能性得到了使用非甾体抗炎药（NSAID）实验结果的间接支持。一般而言，这些药物可增强SRS-A的释放（步行者1973; Engineer et al 1978），并且已表明这种作用与前列腺素（PG）生物合成的抑制有关，后者反过来控制SRS-A的产生。然而，最近的证据表明，类固醇和二十碳四炔酸等药物抑制PG生物合成和SRS-A的产生，表明NSAID的增强作用可能是由于花生四烯酸转移到脂氧合酶介导的途径（Burka & Flower 1979;希区柯克1978; Morris et al 1980 a）。最近有报道称，新型抗炎药苯恶洛芬可抑制兔PMN脂氧合酶产生花生四烯酸的羟基酸衍生物（步行者& Dawson 1979），同时具有相对较低的PG环加氧酶抑制活性（Cashin et al 1977）。该通信比较了苯诺布洛芬与另一种脂氧合酶抑制剂BW 755 c（Higgs et al 1979）以及两种强效PG环氧合酶抑制剂吲哚美辛和吡罗昔康（Carty et al 1980）对脂氧合酶产物和SRS-A形成的影响。还评估了去甲二氢愈创木酸（NDGA）（一种自由基清除剂和已知的脂氧合酶抑制剂）的作用（Hamberg 1976）。抑制脂氧合酶的活性证明使用完整的引发兔腹膜多形核
Recent evidence has suggested that both 5-hydroxy-6glutathionyl-eicosatetraenoic acid (leukotriene C) and its probable degradation product 5-hydroxy-6-cysteinylglycine eicosatetraenoic acid (leukotriene D) contribute to the biological activity hitherto referred to as slowreacting substance of anaphylaxis (SRS-A) (Orning et al 1980; Morris et a1 1980b). These compounds are believed to derive from 5-hydroperoxy-eicosatetraenoic acid (5-HPETE) produced from the oxygenation of arachidonic acid by a lipoxygenase enzyme (Samuelsson et a1 1979). The possibility of a pivotal role for lipoxygenase activity with regard to SRS-A production has received indirect support from experimental results using nonsteroidal anti-inflammatory drugs (NSAIDs). In general, these drugs enhance SRS-A release (Walker 1973; Engineer et a1 1978), and i t has been suggested that this effect is related to inhibition of prostaglandin (PG) biosynthesis which in turn controls SRS-A production. More recent evidence, however, with drugs such as steroids and eicosatetraynoic acid which inhibit both PG biosynthesis and SRS-A production, has suggested that the enhancement observed with NSAIDs may be due to diversion of arachidonate down a lipoxygenase mediated pathway (Burka & Flower 1979; Hitchcock 1978; Morris et al 1980a). Benoxaprofen, a new anti-inflammatory agent, has recently been reported to inhibit the production of hydroxy-acid derivatives of arachidonic acid by rabbit PMN lipoxygenase enzymes (Walker & Dawson 1979), whilst possessing relatively low PG cyclo-oxygenase inhibitory activity (Cashin et al 1977). This communication compares the effect of benoxaprofen with those of BW755c, another lipoxygenase inhibitor (Higgs et a1 1979), and with two potent P G cyclooxygenase inhibitors, indomethacin and piroxicam (Carty et al 1980) on the formation of both lipoxygenase products and SRS-A. The effect of nordihydroguaiaretic acid (NDGA) a free radical scavenger and known lipoxygenase inhibitor (Hamberg 1976) was also assessed. Inhibition of lipoxygenase activity was demonstrated using intact elicited rabbit peritoneal polymorpho-