Effect of 13-hydroperoxyoctadecadienoic acid on prostaglandin synthesis in rabbit kidney medulla microsomes.

T Fujita, T Nakajima, T Matsuma, H Nishida, S Sakuma, Y Fujimoto
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Abstract

The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE) on the synthesis of prostaglandins (PGs) was examined in rabbit kidney medulla microsomes. Medulla microsomes were incubated with arachidonic acid in 0.1 M-Tris/HCl buffer (pH 8.0) containing reduced glutathione and hydroquinone and the PGE2, PGF2a and PGD2 formed were measured by high-pressure liquid chromatography using 9-anthryldiazomethane for derivatization. Under our incubation conditions rabbit kidney medulla was found to produce mainly PGE2. The addition of 13-HPODE inhibited the production of all three PGs to a similar extent. 13-Hydroxyoctadecadienoic acid did not suppress the formation of PGs, indicating the requirement of the hydroperoxy moiety for the inhibitory effect of 13-HPODE on PG formation. Experiments utilizing the native fatty acid linoleic acid and tert-butyl hydroperoxide suggested the importance of the fatty acid-derived hydroperoxide in PG synthesis by kidney medulla. We conclude that 13-HPODE is an inhibitor of renomedullary cyclooxygenase and may have functional effects within the kidney.

13-氢过氧十八烯二酸对兔肾髓质微粒体前列腺素合成的影响。
研究了13-氢过氧十八烯二烯酸(13-HPODE)对兔肾髓质微粒体中前列腺素(pg)合成的影响。髓质微粒体与花生四烯酸在含有还原型谷胱甘肽和对苯二酚的0.1 M-Tris/HCl缓冲液(pH 8.0)中孵育,用9-蒽基重氮甲烷衍生,用高压液相色谱法测定生成的PGE2、PGF2a和PGD2。在我们的培养条件下,发现兔肾髓质主要产生PGE2。添加13-HPODE对所有三种pg的产生均有相似程度的抑制作用。13-羟基十八烯二烯酸没有抑制PG的形成,说明13-羟基十八烯二烯酸抑制PG的形成需要过氧化部分。利用天然脂肪酸亚油酸和过氧化氢叔丁基的实验表明,脂肪酸衍生的过氧化氢在肾髓质合成PG中的重要性。我们得出结论,13-HPODE是肾髓性环氧化酶的抑制剂,可能在肾脏内具有功能作用。
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