6,9-deepoxy-6,9,-(phenylimino)-delta 6,8-prostaglandin I1, (U-60,257), a new inhibitor of leukotriene C and D synthesis: in vitro studies.
6,9-deepoxy-6,9,-(phenylimino)-delta 6,8-prostaglandin I1, (U-60,257), a new inhibitor of leukotriene C and D synthesis: in vitro studies.
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6,9-deepoxy-6,9,-(苯基亚氨基)-δ 6,8-前列腺素 I1 (U-60,257)，一种新的白三烯 C 和 D 合成抑制剂：体外研究。
DOI：
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发表时间：
1982
期刊：
影响因子：
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通讯作者：
J. McGuire
中科院分区：
文献类型：
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作者：
Bach Mk;Brashler;Smith Hw;Fitzpatrick Fa;Frank F. Sun;J. McGuire
从大鼠腹膜洗涤中分离的单个核细胞中加入硫代钙、a23187和半胱氨酸，可显著增加血栓素B2 （TxB2）的形成以及白三烯C和D （LT’s）的形成。该系统中LT的形成被6,9-深聚-6,9-（苯基）- δ 6,8-前列腺素I1 （U-60,257）或其甲酯U-56,467 （ID50分别为4.6和0.31微米）所抑制。对TxB2的形成无抑制作用。相比之下，两种结构相关的化合物PGI2及其稳定的类似物6- β - pgi1不影响LT's或TxB2的形成。从细胞中去除该化合物后，U-60,257对LT形成的抑制作用迅速逆转。u - 60257对人多形核白细胞环加氧酶无抑制作用。它也不能抑制人血小板中12- l -羟基-5,8,10,14-二十碳四烯酸（12-HETE）的形成。另一方面，U-60,257抑制大鼠嗜碱性白血病细胞谷胱甘肽s -转移酶活性（ID50, 37 microM），提示该化合物可能抑制LTC生物合成的最后一步。除了抑制LT合成外，u - 60257似乎也是LT对豚鼠回肠作用的竞争性抑制剂，尽管这种抑制需要比在u - 60257处理的培养皿中检测LT时通常遇到的药物浓度更高的药物浓度。
Addition of the calcium inophore, A 23187, and cysteine to isolated mononuclear cells from rat peritoneal washings causes a marked increase in the formation of thromboxane B2 (TxB2) along with the formation of leukotrienes C and D (LT's). The formation of LT's in this system was inhibited by 6,9-deepoxy-6,9-(phenylimino)-delta 6,8-prostaglandin I1, U-60,257, or its methyl ester, U-56,467, (ID50 4.6 and 0.31 microM, respectively). There was no inhibition of TxB2 formation. By contrast, two structurally-related compounds, PGI2 and its stable analog, 6-beta-PGI1, did not affect the formation of either LT's or TxB2. The inhibition of LT formation by U-60,257 was rapidly reversed after removal of this compound from the cells. U-60,257 did not inhibit the cyclooxygenase of human polymorphonuclear leukocytes. Nor did it inhibit formation of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) in human platelets. On the other hand, U-60,257 inhibited glutathione S-transferase activity of rat basophil leukemia cells (ID50, 37 microM), suggesting that this compound may inhibit the last step in LTC biosynthesis. In addition to inhibiting LT synthesis, U-60,257 also appears to be a competitive inhibitor of the action of LT on the guinea pig ileum, although this inhibition requires a higher drug concentration than those ordinarily encountered during assay for LT's in U-60,257-treated incubations.