Induction studies on the functional heterogeneity of rat liver UDP-glucuronosyltransferases.
Induction studies on the functional heterogeneity of rat liver UDP-glucuronosyltransferases.
复制标题
大鼠肝脏UDP-葡萄糖醛酸基转移酶功能异质性的诱导研究。
DOI：
10.1016/0041-008x(82)90240-x
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发表时间：
1982
影响因子：
3.8
通讯作者：
Klaassen,CD
中科院分区：
文献类型：
--
作者：
Watkins,JB;Gregus,Z;Thompson,TN;Klaassen,CD
苯巴比妥（PB）和3-甲基胆蒽（3-MC）的差异诱导表明至少有两种功能不同的UDP葡萄糖醛酸转移酶（UDP-GT），它们具有不同的受体选择性。一种形式由3-MC诱导，并优先缀合第1组受体，如对硝基苯酚和1-萘酚。另一种UDP-GT是由PB和葡萄糖醛酸第2组苷元、吗啡和氯霉素诱导的。为了进一步研究这种功能异质性，用以下微粒体酶诱导剂预处理雄性Sprague-Dawley大鼠：7，8-苯并吡喃酮（BF）;苯并（a）芘（BP）; 3-MC; 2，3，7，8-四氯二苯并-对-二恶英（TCDD）;丁基羟基茴香醚（BHA）;异黄樟素; PB;双烯醇酮-16 α-腈（PCN）;反式二苯乙烯氧化物（TSO）。用9种受体测定诱导对UDP-GT活性的影响。3-MC增加了第1组糖苷配基萘酚和对硝基苯酚的结合（分别为185%和80%），而PB无效。第2组受体吗啡和氯霉素的结合被PB刺激（分别为120%和250%），而3-MC几乎没有影响。BP和TCDD增强第1组苷元的葡萄糖醛酸化。ISF和TSO诱导两个受体基团的缀合，但对第2组更有效。BF和BHA对UDP-GT活性的影响可忽略不计。由于丙戊酸的葡萄糖醛酸化仅通过PB和TSO处理增加，因此该糖苷配基可能是第2组受体。PB（200%）和PCN（1200%）可刺激洋地黄毒苷-单洋地黄毒苷（DIG）结合。PCN不诱导第1组受体的葡萄糖醛酸化，但对第2组糖苷配基有轻微影响（氯霉素和吗啡分别为130%和40%）。PCN预处理大鼠的DIG结合增加12倍，表明PCN可能诱导另一组（形式）UDP-GT，其优先葡萄糖醛酸化DIG。各组受体内UDP-GT活性的差异诱导表明转移酶可能具有额外的异质性。
Differential induction with phenobarbital (PB) and 3-methylcholanthrene (3-MC) suggests at least two functionally distinct UDP glucuronosyltransferases (UDP-GT) which have different acceptor selectivities. One form is induced by 3-MC and preferentially conjugates group 1 acceptors, such as p-nitrophenol and 1-naphthol. Another UDP-GT is induced by PB and glucuronidates group 2 aglycones, morphine and chloramphenicol. To further study this functional heterogeneity, male Sprague-Dawley rats were pretreated with the following microsomal enzyme inducers: 7,8-benzoflavone (BF); benzo(a)pyrene (BP); 3-MC; 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); butylated hydroxyanisole (BHA); isosafrole; PB; pregnenolone-16α-carbonitrile (PCN); trans-stilbene oxide (TSO). The effect of induction on UDP-GT activity was determined with nine acceptors. Conjugation of group 1 aglycones, naphthol and p-nitrophenol, was increased by 3-MC (185 and 80%, respectively) whereas PB was ineffective. Conjugation of group 2 acceptors, morphine and chloramphenicol, was stimulated by PB (120 and 250%, respectively) while 3-MC had little effect. BP and TCDD enhanced glucuronidation of group 1 aglycones. ISF and TSO induced conjugation of both acceptor groups but were more effective for group 2. BF and BHA had negligible effects on UDP-GT activity. Since glucuronidation of valproic acid was increased only by PB and TSO treatment, this aglycone is probably a group 2 acceptor. Conjugation of digitoxigenin-monodigitoxoside (DIG) was stimulated by PB (200%) and PCN (1200%). PCN did not induce glucuronidation of group 1 acceptors but did have a slight effect on group 2 aglycones (130 and 40% for chloramphenicol and morphine, respectively). The 12-fold increase in DIG conjugation by PCN pretreated rats suggests that PCN may induce another group (form) of UDP-GT which preferentially glucuronidates DIG. Differential induction of UDP-GT activities within each group of acceptors indicates possible additional heterogeneity of the transferase.