Wolff T, Strecker M
Biochem Pharmacol. 1985 Aug 1;34(15):2593-8. doi: 10.1016/0006-2952(85)90553-2.
The effect of various inhibitors and inducers of cytochrome P-450 on the activity of microsomal debrisoquine 4-hydroxylation (DQH) was investigated in rat liver. DQH was strongly inhibited by SKF 525-A, 7,8-benzoflavone, and metyrapone. Pretreatment of animals with common inducers, such as phenobarbital, 3-methylcholanthrene, the commercial PCB mixture, Clophen A-50, dexamethasone and pregenenolone-16 alpha-carbonitrile did not lead to induction of DQH, while most reference reactions, i.e. aldrin epoxidation, ethylmorphine demethylation, and benzo(a)-pyrene hydroxylation were induced under these conditions. DQH likewise was not induced by pretreatment of animals with the enzyme substrate DQ. The relationship between DQH and other cytochrome P-450 functions was also studied in untreated animals. Both genders of Wistar rats exhibited similar rates of DQH, but different activities of the reference reactions. DQH activity in Wistar females however, was 10 times higher than in females of the DA-strain, whereas the reference activities were similar in both strains. The studies were also extended to human liver. DQH activity in homogenates of various biopsy samples was neither correlated to the activity of aldrin epoxidation nor to AHH activity. The results indicate that DQH in the rat and in man reflects the activity of a cytochrome P-450 species not related to various other known cytochrome P-450 functions.
在大鼠肝脏中研究了细胞色素P - 450的各种抑制剂和诱导剂对微粒体去甲异喹胍4 - 羟化（DQH）活性的影响。SKF 525 - A、7,8 - 苯并黄酮和甲吡酮对DQH有强烈抑制作用。用常见诱导剂如苯巴比妥、3 - 甲基胆蒽、商业多氯联苯混合物Clophen A - 50、地塞米松和孕烯醇酮 - 16α - 腈预处理动物，并未导致DQH的诱导，而在这些条件下大多数参考反应，即艾氏剂环氧化、乙基吗啡去甲基化和苯并(a)芘羟化均被诱导。用酶底物DQ预处理动物同样不会诱导DQH。在未处理的动物中也研究了DQH与其他细胞色素P - 450功能之间的关系。两种性别的Wistar大鼠表现出相似的DQH速率，但参考反应的活性不同。然而，Wistar雌性大鼠的DQH活性比DA品系雌性大鼠高10倍，而两种品系的参考活性相似。研究还扩展到了人肝脏。各种活检样品匀浆中的DQH活性既与艾氏剂环氧化活性无关，也与AHH活性无关。结果表明，大鼠和人类中的DQH反映了一种与其他各种已知细胞色素P - 450功能无关的细胞色素P - 450种类的活性。
