Peskar B M, Kozuschek W, Morgenroth K, Hoppe U, Dreyling K W, Peskar B A
Wien Klin Wochenschr. 1986 Feb 21;98(4):98-104.
Tissues of the gastrointestinal tract synthesize leukotriene (LT) B4 and the sulfidopeptide-leukotrienes LTC4, LTD4 and LTE4 from endogenous substrate. Formation of leukotrienes was demonstrated using radioimmunoassay, high pressure liquid chromatography (HPLC) and bioassay. Under basal conditions the gastrointestinal tissues released minor amounts of leukotrienes only. Formation of lipoxygenase-derived products of arachidonic acid metabolism was, however, significantly increased in the presence of various stimuli. Thus, significant amounts of LTB4 and of sulfidopeptide-leukotrienes were released from colonic and gastric mucosa of guinea-pigs sensitized against ovalbumin when incubations were carried out in the presence of antigen. Antigen-induced leukotriene formation was not found in the muscularis propria and subserosal of ovalbumin-sensitized guinea-pigs. Release of cyclooxygenase-derived metabolites of arachidonic acid, on the other hand, was most abundant in the subserosal layer of the guinea-pig colon and was not influenced by the immunological reaction. Inhibitors of cyclooxygenase, such as indomethacin, reduced gastrointestinal formation of prostaglandins, but not of leukotrienes. Inhibitors of 5-lipoxygenase, however, significantly decreased leukotriene formation. Synthesis of LTB4 and of sulfidopeptide-leukotrienes was also found in human colonic mucosal tissue, using the divalent cation-ionophore A23187 as stimulating agent. HPLC analysis demonstrated that the sulfidopeptide-leukotrienes released were composed of a mixture of LTC4, LTD4 and LTE4. In addition, human colonic mucosal tissue contained high activities of enzymes that rapidly convert LTC4 to LTE4. As in most biological systems LTE4 is less active than LTC4 and LTD4 degrading enzymes might represent a local inactivating mechanism. Mucosal tissue of patients with Crohn's disease synthesized considerably more LTB4 and sulfidopeptide-leukotrienes than non-inflamed mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
胃肠道组织可利用内源性底物合成白三烯（LT）B4以及含硫肽白三烯LTC4、LTD4和LTE4。白三烯的形成通过放射免疫测定、高压液相色谱（HPLC）和生物测定得以证实。在基础条件下，胃肠道组织仅释放少量白三烯。然而，在各种刺激存在时，花生四烯酸代谢的脂氧合酶衍生产物的形成显著增加。因此，当在抗原存在下进行孵育时，对卵清蛋白致敏的豚鼠结肠和胃黏膜会释放大量的LTB4和含硫肽白三烯。在对卵清蛋白致敏的豚鼠固有肌层和浆膜下层未发现抗原诱导的白三烯形成。另一方面，花生四烯酸的环氧化酶衍生代谢产物的释放，在豚鼠结肠浆膜下层最为丰富，且不受免疫反应影响。环氧化酶抑制剂，如消炎痛，可减少胃肠道前列腺素的形成，但对白三烯无影响。然而，5-脂氧合酶抑制剂可显著降低白三烯形成。使用二价阳离子载体A23187作为刺激剂时，在人结肠黏膜组织中也发现了LTB4和含硫肽白三烯的合成。HPLC分析表明，释放的含硫肽白三烯由LTC4、LTD4和LTE4的混合物组成。此外，人结肠黏膜组织含有高活性的酶，可迅速将LTC4转化为LTE4。与大多数生物系统一样，LTE4活性低于LTC4，降解酶可能代表一种局部失活机制。克罗恩病患者的黏膜组织合成的LTB4和含硫肽白三烯比未发炎黏膜多得多。（摘要截短于250字）
