Regulation of arachidonic acid metabolism by cytochrome P-450 in rabbit kidney.
Regulation of arachidonic acid metabolism by cytochrome P-450 in rabbit kidney.
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DOI：
10.1042/bj2380283
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发表时间：
1986-08
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影响因子：
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通讯作者：
M. Schwartzman;N. Abraham;M. A. Carroll;R. Levere;J. Mcgiff
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文献类型：
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作者：
M. Schwartzman;N. Abraham;M. A. Carroll;R. Levere;J. Mcgiff
兔肾微粒体细胞色素P-450依赖的花生四烯酸代谢与细胞色素P-450水平相关。血红素加氧酶的诱导剂钴降低了皮质和髓质中的细胞色素P-450，同时芳烃羟基酶(细胞色素P-450的活性指数)减少了2倍，肾微粒体(微体部分)形成依赖细胞色素P-450的花生四烯酸代谢产物的减少也类似。后者的形成完全依赖于NADPH的加入，并被细胞色素P-450依赖酶的抑制剂SKF-525A阻止。用气相色谱-质谱法鉴定了皮质微粒体的花生四烯酸代谢产物。分别为20-和19-羟基二十碳四烯酸、11，12-环氧二十碳三烯酸和11，12-二羟基二十碳三烯酸。髓质微粒体的花生四烯酸代谢产物的分布是相同的。3-甲基胆蒽和β-萘黄酮诱导的细胞色素P-450使皮质和延髓的细胞色素P-450含量和芳烃羟基酶活性增加2倍，这与通过细胞色素P-450途径产生的花生四烯酸代谢产物增加2倍有关。这些变化也可以在从Henle环粗大的升支的髓质段分离出来的细胞中得到证明，以前的研究表明，这些细胞专门通过细胞色素P-450依赖的途径代谢花生四烯酸。通过这一途径形成花生四烯酸代谢产物的比活性在肾脏高于肝脏，最高活性在外髓，即7.9微克，而从外髓和肝脏获得的微体每30分钟细胞色素P-450转化的花生四烯酸为2.5微克。这些发现与高水平的细胞色素P-450同工酶(S)是一致的，该酶专用于花生四烯酸代谢，主要定位于外髓。
Renal microsomal cytochrome P-450-dependent arachidonic acid metabolism was correlated with the level of cytochrome P-450 in the rabbit kidney. Cobalt, an inducer of haem oxygenase, reduced cytochrome P-450 in both the cortex and medulla in association with a 2-fold decrease in aryl-hydrocarbon hydroxylase, an index of cytochrome P-450 activity, and a similar decrease in the formation of cytochrome P-450-dependent arachidonic acid metabolites by renal microsomes (microsomal fractions). Formation of the latter was absolutely dependent on NADPH addition and was prevented by SKF-525A, an inhibitor of cytochrome P-450-dependent enzymes. Arachidonate metabolites of cortical microsomes were identified by g.c.-m.s. as 20- and 19-hydroxyeicosatetraenoic acid, 11,12-epoxyeicosatrienoic acid and 11,12-dihydroxyeicosatrienoic acid. The profile of arachidonic acid metabolites was the same for the medullary microsomes. Induction of cytochrome P-450 by 3-methylcholanthrene and beta-naphthoflavone increased cytochrome P-450 content and aryl-hydrocarbon hydroxylase activity by 2-fold in the cortex and medulla, and this correlated with a 2-fold increase in arachidonic acid metabolites via the cytochrome P-450 pathway. These changes can also be demonstrated in cells isolated from the medullary segment of the thick ascending limb of the loop of Henle, which previously have been shown to metabolize arachidonic acid specifically via the cytochrome P-450-dependent pathway. The specific activity for the formation of arachidonic acid metabolites by this pathway is higher in the kidney than in the liver, the highest activity being in the outer medulla, namely 7.9 microgram as against 2.5 micrograms of arachidonic acid transformed/30 min per nmol of cytochrome P-450 for microsomes obtained from outer medulla and liver respectively. These findings are consistent with high levels of cytochrome P-450 isoenzyme(s), specific for arachidonic acid metabolism, primarily localized in the outer medulla.