LEUKOTRIENE SYNTHESIS BY HUMAN GASTROINTESTINAL TISSUES
LEUKOTRIENE SYNTHESIS BY HUMAN GASTROINTESTINAL TISSUES
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DOI：
10.1016/0005-2760(86)90145-1
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发表时间：
1986-09-12
期刊：
影响因子：
--
通讯作者：
PESKAR, BM
中科院分区：
文献类型：
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作者：
DREYLING, KW;HOPPE, U;PESKAR, BM
用放射免疫法测定前列腺素E_2、白三烯B_4和硫肽白三烯，研究了手术中获得的人胃肠道组织的前列腺素和白三烯合成能力。通过高压液相色谱法（HPLC）验证了白三烯免疫测定数据。在37 ℃孵育期间，C，人胃、空回肠和结肠粘膜碎片释放的前列腺素E2比白三烯B4和硫肽白三烯的量大得多。胃肠道平滑肌组织释放甚至更大量的前列腺素E2，但较少量的白三烯比相应的粘膜组织。与正常结肠粘膜相比，腺癌组织释放大量的白三烯B4、硫肽白三烯和前列腺素E2。离子载体A23187（5 μ g/ml）不刺激前列腺素E2从所研究的任何组织中的释放，但增强了几乎完全与标准白三烯B4共层析的白三烯B4的释放，而免疫反应性硫肽白三烯由白三烯C4、D4和E4的混合物组成。用脂氧合酶抑制剂去甲二氢愈创木酸（NDGA）和双酶抑制剂BW 755 C（3-氨基-1-（三氟甲基苯基）-2-吡唑啉盐酸盐）抑制人胃肠组织的白三烯合成。前列腺素E2的合成受到环氧化酶抑制剂吲哚美辛和BW 755 C的抑制。孵育的胃肠道组织中谷胱甘肽的存在下，减少了白三烯D4和E4的量，而释放的白三烯C4同时增加。另一方面，氚化白三烯C4与来自人胃或结肠粘膜的孵育介质孵育导致底物转化为[3 H]白三烯D4和[3 H]白三烯E4。结果表明，人类胃肠道组织的能力，合成5-脂氧合酶衍生的产品的花生四烯酸代谢，白三烯B4和硫肽白三烯，除了大量的前列腺素E2。此外，硫肽白三烯代谢酶γ-在人胃肠道组织中检测到谷氨酰转肽和二肽酶。这些酶可能在人胃肠道产生的硫肽白三烯的生物失活和/或生物学特性改变中起重要作用。
The prostaglandin and leukotriene synthesizing capacity of human gastrointestinal tissues obtained at surgery was investigated using radioimmunoassays for prostaglandin E2, leukotriene B4 and sulfidopeptide leukotrienes. The leukotriene immunoassay data were validated by high-pressure liquid chromatography (HPLC). During incubation at 37.degree. C, fragments of human gastric, jejuno-ileal and colonic mucosa released considerably larger amounts of prostaglandin E2 than of leukotriene B4 and sulfidopeptide leukotrienes. Gastrointestinal smooth muscle tissues released even larger amounts of prostaglandin E2, but smaller amounts of leukotrienes than the corresponding mucosal tissues. Adenocarcinoma tissue released larger amounts of leukotriene B4, sulfidopeptide leukotrienes and prostaglandin E2 than normal colonic mucosa. Ionophore A23187 (5 .mu.g/ml) did not stimulate release of prostaglandin E2 from any of the tissues investigated, but enhanced release of leukotriene B4 co-chromatographed almost exclusively with standard leukotriene B4, while immunoreactive sulfidopeptide leukotrienes consisted of a mixture of leukotrienes C4, D4 and E4. Leukotriene synthesis by human gastrointestinal tissues was inhibited by the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) and the dual enzyme inhibitor BW755C (3-amino-1-(trifluoromethylphenyl)-2-pyrazoline hydrochloride). Synthesis of prostaglandin E2 was inhibited by the cycloxygenase inhibitor indomethacin as well as by BW755C. Incubation of gastrointestinal tissues in the presence of glutathione decreased the amounts of leukotrienes D4 and E4, while release of leukotriene C4 was simultaneously increased. On the other hand, incubation of tritiate leukotriene C4 with incubation media from human gastric or colonic mucosa resulted in conversion of the substrate to [3H]leukotriene D4 and [3H]leukotriene E4. The results indicate the capacity of human gastrointestinal tissues to synthesize the 5-lipoxygenase-derived products of arachidonate metabolism, leukotriene B4 and sulfidopeptide leukotrienes, in addition to larger amounts of prostaglandin E2. Furthermore, considerable activities of the sulfidopeptide leukotriene-metabolizing enzymes .gamma.-glutamyl transpeptide and dipeptidase were detected in human gastrointestinal tissues. The enzymes might play an important role in biological inactivation and/or change of biological profile of sulfidopeptide leukotrienes generated in the human gastrointestinal tract.