Simmet T, Aissa J, Sutter D, Juan H, Peskar B A
Naunyn Schmiedebergs Arch Pharmacol. 1987 Jun;335(6):652-9. doi: 10.1007/BF00166982.
Exogenous eicosapentaenoic acid (EPA, 16.5 mumol/l or 33 mumol/l) inhibited dose-dependently the anaphylactic contractile response of guinea-pig lung parenchymal strips suspended in an organ bath. As determined by radioimmunoassay, EPA inhibited in a dose-dependent manner the anaphylactic release of the cyclooxygenase products thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1 alpha but simultaneously enhanced the release of sulfidopeptide (SP)-leukotrienes (LT). Indomethacin (2.8 mumol/l) abolished the release of cyclooxygenase products but potentiated the release of SP-LT. However, indomethacin treatment did not affect the inhibitory action of EPA on the contractile response of the anaphylactic lung strips. The lipoxygenase inhibitor, esculetin (50 mumol/l), inhibited the release of SP-LT and also that of cyclooxygenase products of polyunsaturated fatty acid metabolism. The combination of esculetin and EPA resulted in enhanced inhibition of the anaphylactic contractile response as compared to EPA alone. By reversed phase high pressure liquid chromatography (HPLC), SP-LT from anaphylactic lung parenchymal strips was shown to consist of LTD4 and LTE4. EPA-pretreated lung strips released upon immunologic challenge additional immunoreactivity comigrating with authentic LTC4, LTC5, LTD5 and LTE5. While anaphylactic control strips also released LTB4, in the bath fluid of EPA-treated strips, an additional immunoreactive compound migrating with the retention time of LTB5 was observed. In non-sensitized guinea-pig lung parenchymal strips EPA inhibited the myotropic activity of exogenous mediators such as histamine (9 mumol/l), LTC4 (16 nmol/l) and the TX mimetic U 46619 (28.4 nmol/l), an effect which was neither affected by indomethacin (2.8 mumol/l) nor by the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
外源性二十碳五烯酸（EPA，16.5微摩尔/升或33微摩尔/升）以剂量依赖的方式抑制悬浮于器官浴中的豚鼠肺实质条带的过敏收缩反应。通过放射免疫测定确定，EPA以剂量依赖的方式抑制环氧化酶产物血栓素（TX）B2和6-酮-前列腺素（PG）F1α的过敏释放，但同时增强了硫肽（SP）-白三烯（LT）的释放。吲哚美辛（2.8微摩尔/升）消除了环氧化酶产物的释放，但增强了SP-LT的释放。然而，吲哚美辛处理并未影响EPA对过敏肺条带收缩反应的抑制作用。脂氧合酶抑制剂七叶亭（50微摩尔/升）抑制了SP-LT的释放以及多不饱和脂肪酸代谢中环氧化酶产物的释放。与单独使用EPA相比，七叶亭和EPA的组合导致对过敏收缩反应的抑制作用增强。通过反相高压液相色谱（HPLC）显示，过敏肺实质条带中的SP-LT由LTD4和LTE4组成。经EPA预处理的肺条带在免疫攻击后释放出与天然LTC4、LTC5、LTD5和LTE5共迁移的额外免疫反应性物质。虽然过敏对照条带也释放LTB4，但在经EPA处理的条带的浴液中，观察到一种额外的免疫反应性化合物，其保留时间与LTB5一致。在未致敏的豚鼠肺实质条带中，EPA抑制外源性介质如组胺（9微摩尔/升）、LTC4（16纳摩尔/升）和TX模拟物U 46619（28.4纳摩尔/升）的肌otropic活性，这种作用既不受吲哚美辛（2.8微摩尔/升）的影响，也不受脂氧合酶抑制剂去甲二氢愈创木酸（NDGA，10微摩尔/升）的影响。（摘要截短于250字）
