Dahlén S E, Hedqvist P, Hammarström S, Samuelsson B
Nature. 1980 Dec 4;288(5790):484-6. doi: 10.1038/288484a0.
Slow reacting substance of anaphylaxis (SRS-A) is released by various stimuli, including immunological challenge, and has long been considered an important mediator of immediate hypersensitivity reactions, such as bronchoconstriction in allergic asthma. Recently, slow reacting substances from several tissues have been identified and characterized as members of a newly discovered group of substances, the leukotrienes. Leukotrienes are generated from arachidonic acid and other polyunsaturated fatty acids in a pathway initially involving a lipoxygenase-catalysed oxygenation at C-5 (Fig. 1). This differs from the synthesis of prostaglandins and thromboxanes, where the initial transformation of arachidonic acid is catalysed by a cyclo oxygenase (Fig. 1). Recently, leukotriene C4(LTC4:5(S)-hydroxy,6(R)-S-glutathionyl-7,9-trans, 11,14-cis-eicosatetraenoic acid) and D4(LTD4:5(S)-hydroxy,6(R)-S-cysteinyl-glycyl-7,9-trans,11,14-cis-eicosatetraenoic acid) were found to have biological effects in several bioassay systems, which are strikingly similar to those previously reported for impure extracts of SRS-A. Here we report the remarkable contractile activity of both LTC4 and LTD4 on isolated human bronchi, which further emphasizes the possibility that leukotrienes are potent mediators of bronchoconstriction in man.
过敏反应迟缓反应物质(SRS-A)可由多种刺激释放,包括免疫攻击,长期以来一直被认为是速发型超敏反应的重要介质,如过敏性哮喘中的支气管收缩。最近,已从几种组织中鉴定出迟缓反应物质,并将其表征为一组新发现的物质——白三烯的成员。白三烯由花生四烯酸和其他多不饱和脂肪酸通过一条最初涉及脂氧合酶催化的C-5位氧合作用的途径生成(图1)。这与前列腺素和血栓烷的合成不同,在前列腺素和血栓烷的合成中,花生四烯酸的初始转化由环氧化酶催化(图1)。最近,发现白三烯C4(LTC4:5(S)-羟基,6(R)-S-谷胱甘肽基-7,9-反式,11,14-顺式-二十碳四烯酸)和D4(LTD4:5(S)-羟基,6(R)-S-半胱氨酰甘氨酰-7,9-反式,11,14-顺式-二十碳四烯酸)在几种生物测定系统中具有生物学效应,这些效应与先前报道的SRS-A不纯提取物的效应惊人地相似。在此,我们报告LTC4和LTD4对离体人支气管均具有显著的收缩活性,这进一步强调了白三烯可能是人类支气管收缩的强效介质。