Han Ying, Sugiyama Yuichi
Department of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
Biol Pharm Bull. 2006 May;29(5):1032-5. doi: 10.1248/bpb.29.1032.
Microsomal enzyme inducers are known to influence the expression of many transporter proteins and mRNA. In this study, we examined the effects of microsomal enzyme inducers on the mRNA expression of Breast Cancer Resistance Protein (BCRP) and Multidrug Resistance Associated Protein 2 (MRP2) in BALB/c mice. mRNA expression in liver, duodenum, jejunum and ileum was examined in mice, which were treated with microsomal enzyme inducers-aryl hydrocarbon receptor (AhR) ligands 3-methylcholanthrene (3-MC) and pregnane-x-receptor (PXR) ligand pregenolone-16alpha-carbonitrile (PCN) and compared with control vehicle. The results suggested that the expression level of bcrp mRNA in the ileum was twice that in the liver, duodenum and jejunum using both semi quantitative PCR and Real-time PCR. Mrp2 mRNA was significantly increased by both PCN and 3-MC treatment. In contrast, bcrp mRNA expression was not significantly affected by these inducers. In summary, this study demonstrated that the expression of mrp2 mRNA is regulated by PCN and 3-MC, however, bcrp mRNA expression was not significantly affected by PCN and 3-MC.
已知微粒体酶诱导剂会影响许多转运蛋白和信使核糖核酸（mRNA）的表达。在本研究中，我们检测了微粒体酶诱导剂对BALB/c小鼠乳腺癌耐药蛋白（BCRP）和多药耐药相关蛋白2（MRP2）信使核糖核酸表达的影响。在经微粒体酶诱导剂——芳烃受体（AhR）配体3-甲基胆蒽（3-MC）和孕烷X受体（PXR）配体孕烯醇酮-16α-腈（PCN）处理的小鼠中，检测其肝脏、十二指肠、空肠和回肠中的信使核糖核酸表达，并与对照载体进行比较。结果表明，使用半定量聚合酶链反应（PCR）和实时定量PCR检测时，回肠中bcrp信使核糖核酸的表达水平是肝脏、十二指肠和空肠中的两倍。PCN和3-MC处理均使Mrp2信使核糖核酸显著增加。相比之下，这些诱导剂对bcrp信使核糖核酸的表达没有显著影响。总之，本研究表明，PCN和3-MC可调节mrp2信使核糖核酸的表达，然而，PCN和3-MC对bcrp信使核糖核酸的表达没有显著影响。
