Andersson B, Larsson R, Rahimtula A, Moldéus P
Biochem Pharmacol. 1983 Mar 15;32(6):1045-50. doi: 10.1016/0006-2952(83)90623-8.
p-Phenetidine is metabolized by ram seminal vesicle (RSV) microsomes, horseradish peroxidase (HRP) and rat liver microsomes to protein-binding products. These reactions are very rapid and depend on the presence of arachidonic acid (AA) or various hydroperoxidases. The RSV- and HRP-mediated binding was inhibited more than 80% by the addition of reduced glutathione (1 mM) or the antioxidant butylated hydroxyanisole (0.5 mM). Indomethacin (100 microM) and acetylsalicylic acid (1 mM) reduced the AA-dependent reaction in RSV microsomes to less than 5% of control values. When hydrogen peroxide replaced AA, the RSV/H2O2-supported binding in the presence of 50 microM p-phenetidine proceeded at rates similar to that observed with RSV/AA. Unlike the AA-dependent reaction, the H2O2-supported reaction showed no inhibition of protein binding at higher p-phenetidine concns. The data in this report are consistent with a peroxidatic activation of p-phenetidine possibly involving an amine radical catalyzed by prostaglandin synthase (PGS) present in RSV microsomes as well as by other peroxidases. The mechanism for this activation and physiological implications are discussed.
对乙氧基苯胺可被公羊精囊（RSV）微粒体、辣根过氧化物酶（HRP）和大鼠肝脏微粒体代谢为与蛋白质结合的产物。这些反应非常迅速，且依赖于花生四烯酸（AA）或各种氢过氧化物酶的存在。添加还原型谷胱甘肽（1 mM）或抗氧化剂丁基羟基茴香醚（0.5 mM）可使RSV和HRP介导的结合受到80%以上的抑制。吲哚美辛（100 microM）和乙酰水杨酸（1 mM）可使RSV微粒体中依赖AA的反应降至对照值的5%以下。当用过氧化氢替代AA时，在50 microM对乙氧基苯胺存在下，RSV/H2O2支持的结合速率与RSV/AA观察到的速率相似。与依赖AA的反应不同，H2O2支持的反应在较高对乙氧基苯胺浓度下未显示出对蛋白质结合的抑制作用。本报告中的数据与对乙氧基苯胺的过氧化物激活作用一致，可能涉及RSV微粒体中存在的前列腺素合酶（PGS）以及其他过氧化物酶催化的胺自由基。讨论了这种激活作用的机制及其生理意义。
