Hagenbuch B, Scharschmidt B F, Meier P J
Department of Medicine, University Hospital, Zürich, Switzerland.
Biochem J. 1996 Jun 15;316 ( Pt 3)(Pt 3):901-4. doi: 10.1042/bj3160901.
A Na(+)-dependent bile acid (Na+/taurocholate co-transporting polypeptide; Ntcp) and a Na(+)-independent bromosulphophthalein (BSP)/bile acid uptake system (organic-anion-transporting polypeptide; oatp) have been cloned from rat liver by using functional expression cloning in Xenopus laevis oocytes. To evaluate the extent to which these cloned transporters could account for overall hepatic bile acid and BSP uptake, we used antisense oligonucleotides to inhibit the expression of Ntcp and oatp in Xenopus laevis oocytes injected with total rat liver mRNA. An Ntcp-specific antisense oligonucleotide co-injected with total rat liver mRNA blocked the expression of Na(+)-dependent taurocholate uptake by approx. 95%. In contrast, an oatp-specific antisense oligonucleotide when co-injected with total rat liver mRNA had no effect on the expression of Na(+)-dependent taurocholate uptake, but it blocked Na(+)-independent uptake of taurocholate by approx. 80% and of BSP by 50%. Assuming similar expression of hepatocellular bile acid and organic anion transporters in Xenopus laevis oocytes, these results indicate that Ntcp and oatp respectively represent the major, if not the only, Na(+)-dependent and Na(+)-independent taurocholate uptake systems in rat liver. By contrast, the cloned oatp accounts for only half of BSP transport, suggesting that there must be additional, non-bile acid transporting organic anion uptake systems in rat liver.
通过在非洲爪蟾卵母细胞中进行功能表达克隆，已从大鼠肝脏中克隆出一种钠依赖性胆汁酸转运体（钠/牛磺胆酸盐共转运多肽；Ntcp）和一种钠非依赖性溴磺酞钠（BSP）/胆汁酸摄取系统（有机阴离子转运多肽；oatp）。为了评估这些克隆的转运体在多大程度上能够解释肝脏对胆汁酸和BSP的整体摄取情况，我们使用反义寡核苷酸抑制注射了大鼠肝脏总mRNA的非洲爪蟾卵母细胞中Ntcp和oatp的表达。与大鼠肝脏总mRNA共注射的Ntcp特异性反义寡核苷酸使钠依赖性牛磺胆酸盐摄取的表达被阻断了约95%。相比之下，与大鼠肝脏总mRNA共注射的oatp特异性反义寡核苷酸对钠依赖性牛磺胆酸盐摄取的表达没有影响，但它使牛磺胆酸盐的钠非依赖性摄取被阻断了约80%，使BSP的摄取被阻断了50%。假设非洲爪蟾卵母细胞中肝细胞胆汁酸和有机阴离子转运体的表达情况相似，这些结果表明，Ntcp和oatp分别代表大鼠肝脏中主要的（即便不是唯一的）钠依赖性和钠非依赖性牛磺胆酸盐摄取系统。相比之下，克隆的oatp仅占BSP转运的一半，这表明大鼠肝脏中必定存在其他非胆汁酸转运的有机阴离子摄取系统。
