Koopen N R, Wolters H, Müller M, Schippers I J, Havinga R, Roelofsen H, Vonk R J, Stieger B, Meier P J, Kuipers F
Groningen Institute for Drug Studies, University Hospital Groningen, The Netherlands.
J Hepatol. 1997 Oct;27(4):699-706. doi: 10.1016/s0168-8278(97)80087-6.
BACKGROUND/AIMS: Efficient uptake at the basolateral plasma membrane of hepatocytes is required for maintenance of the enterohepatic circulation of bile salts. Uptake occurs mainly via a Na+-dependent process mediated by ntcp, a recently cloned and characterized 51 kDa glycoprotein. The aim of this study was to evaluate the role of variations in hepatic bile salt flux through the liver in the regulation of ntcp activity and expression under non-cholestatic conditions.
We determined the kinetics of Na+-dependent taurocholate transport in isolated basolateral plasma membrane vesicles as well as hepatic ntcp protein and ntcp mRNA levels in long-term (8 days) bile-diverted rats, with a transhepatic bile salt flux of 0, and in streptozotocin-induced diabetic rats with a 2.5-fold increased bile salt flux.
We found no changes in the kinetics of taurocholate transport in the absence of transhepatic bile salt flux due to bile diversion. Ntcp protein and ntcp mRNA levels were also unaffected in bile-diverted rats. Likewise, no changes in taurocholate transport kinetics, ntcp protein or ntcp mRNA levels were detected in streptozotocin-diabetic rats when compared to non-diabetic controls. Thus, variation in hepatic bile salt flux from 0 to 250% of normal values had no effect on hepatic ntcp expression or taurocholate transport activity in basolateral plasma membrane vesicles in rats. In contrast, 4 days of bile duct ligation resulted in a strong decrease in ntcp mRNA and protein levels, as recently also reported by others.
Our data indicate that ntcp is not regulated by the transhepatic flux of bile acids under non-cholestatic conditions.
背景/目的：维持胆盐的肠肝循环需要肝细胞基底外侧质膜进行高效摄取。摄取主要通过由ntcp介导的钠依赖性过程发生，ntcp是一种最近克隆并鉴定的51 kDa糖蛋白。本研究的目的是评估在非胆汁淤积条件下，肝脏中胆盐通量变化在ntcp活性和表达调节中的作用。
我们测定了长期（8天）胆汁转流大鼠（经肝胆盐通量为0）以及链脲佐菌素诱导的糖尿病大鼠（胆盐通量增加2.5倍）分离的基底外侧质膜囊泡中钠依赖性牛磺胆酸盐转运的动力学，以及肝脏ntcp蛋白和ntcp mRNA水平。
我们发现，由于胆汁转流导致经肝胆盐通量缺失时，牛磺胆酸盐转运动力学没有变化。胆汁转流大鼠的ntcp蛋白和ntcp mRNA水平也未受影响。同样，与非糖尿病对照组相比，链脲佐菌素诱导的糖尿病大鼠中未检测到牛磺胆酸盐转运动力学、ntcp蛋白或ntcp mRNA水平的变化。因此，大鼠肝脏胆盐通量从正常值的0变化到250%，对肝脏ntcp表达或基底外侧质膜囊泡中的牛磺胆酸盐转运活性没有影响。相比之下，胆管结扎4天导致ntcp mRNA和蛋白水平大幅下降，其他人最近也有相关报道。
我们的数据表明，在非胆汁淤积条件下，ntcp不受胆汁酸经肝通量的调节。
