Glucuronide formation of various drugs in liver microsomes and in isolated hepatocytes from phenobarbital- and 3-methylcholanthrene-treated rats.
Glucuronide formation of various drugs in liver microsomes and in isolated hepatocytes from phenobarbital- and 3-methylcholanthrene-treated rats.
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苯巴比妥和 3-甲基胆蒽治疗大鼠的肝微粒体和分离肝细胞中各种药物的葡萄糖苷酸形成。
DOI：
10.1016/0006-2952(84)90375-7
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发表时间：
1984
影响因子：
5.8
通讯作者：
K. Bock
中科院分区：
文献类型：
--
作者：
D. Ullrich;K. Bock
大鼠肝微粒体udp -葡萄糖醛基转移酶的各种底物在体外被分类为3-甲基胆蒽或苯巴比妥诱导酶形式的首选底物。微粒体对第三组底物（包括雌酮、酚酞、对乙酰氨基酚和恶西泮）的udp -葡萄糖醛基转移酶活性没有被3-甲基胆蒽或苯巴比妥治疗显著改变。选择了一些具有3-甲基胆蒽和苯巴比妥诱导酶活性的底物，以评估多种酶形式对完整细胞中葡萄糖醛酸盐形成的重要性。这些化合物的代谢在未处理的对照和3-甲基胆蒽（mc -肝细胞）或苯巴比妥（pb -肝细胞）处理的大鼠分离的肝细胞中进行比较。1-萘酚和3-羟基苯并[a]芘的糖醛酸化主要在mc -肝细胞中增强（bbb - 2倍），而氯霉素和胆红素的糖醛酸化主要在pb -肝细胞中增强。这些观察结果与体外udp -葡萄糖醛酸转移酶活性的差异诱导一致，表明除了辅助因子供应、生理激活剂等其他因素外，多种酶形式的水平对完整细胞中葡萄糖醛酸的形成起关键作用。
Various substrates of rat liver microsomal UDP-glucuronosyltransferase were classifiedin vitroas preferred substrates of either 3-methylcholanthrene- or phenobarbital-inducible enzyme forms. Microsomal UDP-glucuronosyltransferase activities towards a third group of substrates (including oestrone, phenolphthalein, paracetamol and oxazepam) are not markedly altered by treatment with either 3-methylcholanthrene or phenobarbital. Some substrates of the 3-methylcholanthrene- and phenobarbital-inducible enzyme activities were selected to evaluate the importance of multiple enzyme forms for glucuronide formation in the intact cell. The metabolism of these compounds was compared in isolated hepatocytes from untreated controls and from rats treated with 3-methylcholanthrene (MC-hepatocytes) or phenobarbital (PB-hepatocytes). Glucuronidation of 1-naphthol and 3-hydroxy-benzo[a]pyrene was chiefly enhanced in MC-hepatocytes (> 2-fold), whereas glucuronidation of chloramphenicol and bilirubin was chiefly enhanced in PB-hepatocytes. These observations are in agreement with differential induction of UDP-glucuronosyltransferase activitiesin vitrosuggesting that, besides other factors such as cofactor supply, physiological activators, etc., the levels of the multiple enzyme forms are critically determining glucuronide formation in the intact cell.
对硝基苯酚在灌注大鼠肝脏中的结合：底物浓度和碳水化合物储备的影响。
DOI：
--
发表时间：
1981
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Reinke,LA;Belinsky,SA;Evans,RK;Kauffman,FC;Thurman,RG
通讯作者：
Thurman,RG