Hagenbuch B, Meier P J
Department of Internal Medicine, University Hospital, Zürich/Switzerland.
Semin Liver Dis. 1996 May;16(2):129-36. doi: 10.1055/s-2007-1007226.
Sinusoidal (basolateral) bile sale uptake is mediated by Na(+)-dependent and Na(+)-independent transport systems. Two hepatocellular bile salt uptake systems have been cloned from rat and human livers. The Na(+)-taurocholate cotransporting polypeptides Ntcp and NTCP mediate strictly Na(+)-dependent bile salt uptake into rat and human hepatocytes, respectively. Extensive characterization of Ntcp expression and function in a variety of eukaryotic cell lines, cultured hepatocytes, and intact rat liver indicates that Ntcp can account for most, if not all, Na(+)-dependent bile salt transport functions in rat liver. Whether the same is also true for the human NTCP is less well understood. The Na(+)-independent organic anion transporting polypeptides oatpl (rat) and OATP (human) exhibit a wide and charge-independent substrate specificity. Their transported substrates include sulfobromophthalein, bile salts, estrone-3-sulfates, ouabain, and other neutral steroids, as well as certain amphipathic organic cations. Its broad and charge-independent substrate specificity indicates that oatpl represents the previously suggested hepatocellular "multispecific bile salt transporter.". Oatpl and OATP are also expressed in the kidney and brain. Whether there are additional oatpl- and OATP-related proteins involved in overall hepatic drug and steroid clearance remains to be determined.
窦状隙（基底外侧）胆盐摄取由钠依赖性和非钠依赖性转运系统介导。已从大鼠和人类肝脏中克隆出两种肝细胞胆盐摄取系统。钠-牛磺胆酸盐共转运多肽Ntcp和NTCP分别介导大鼠和人类肝细胞中严格依赖钠的胆盐摄取。对Ntcp在多种真核细胞系、培养的肝细胞和完整大鼠肝脏中的表达及功能进行的广泛表征表明，Ntcp可解释大鼠肝脏中大部分（如果不是全部）依赖钠的胆盐转运功能。人类NTCP是否也是如此则了解较少。非钠依赖性有机阴离子转运多肽oatpl（大鼠）和OATP（人类）表现出广泛且不依赖电荷的底物特异性。它们转运的底物包括磺溴酞钠、胆盐、雌酮-3-硫酸盐、哇巴因和其他中性类固醇，以及某些两亲性有机阳离子。其广泛且不依赖电荷的底物特异性表明oatpl代表了先前提出的肝细胞“多特异性胆盐转运体”。oatpl和OATP在肾脏和大脑中也有表达。是否存在其他与oatpl和OATP相关的蛋白质参与肝脏整体药物和类固醇清除仍有待确定。
