Ganguly T C, Liu Y, Hyde J F, Hagenbuch B, Meier P J, Vore M
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington 40536.
Biochem J. 1994 Oct 1;303 ( Pt 1)(Pt 1):33-6. doi: 10.1042/bj3030033.
We have shown that Na+/taurocholate co-transport activity is decreased in pregnancy, but rebounds post partum relative to non-pregnant controls, and that activity can be increased by treatment with ovine prolactin [Ganguly, Hyde and Vore (1993) J. Pharmacol. Exp. Ther. 267, 82-87]. To determine the basis for these effects, Na+/taurocholate co-transport was determined in purified basolateral liver plasma-membrane (bLPM) vesicles and compared with steady-state mRNA levels encoding the Na+/taurocholate-co-transporting polypeptide (Ntcp) in non-pregnant controls, pregnant rats (19-20 days pregnant), rats post partum (48 h post partum) and rats post partum treated with bromocriptine to inhibit prolactin secretion. Na+/taurocholate co-transport activity (nmol/5 s per mg of protein) in bLPM was decreased from 10.4 +/- 1.8 in non-pregnant controls to 7.9 +/- 0.6 in bLPM in pregnant rats, but rebounded to 17.5 +/- 1.3 post partum; treatment of rats post partum with bromocriptine to inhibit prolactin secretion decreased activity to 14.1 +/- 0.9. Northern and slot-blot analyses revealed similar changes in mRNA for Ntcp, so that a positive correlation was observed between Na+/taurocholate co-transport activity and Ntcp mRNA. Furthermore, treatment of ovariectomized rats with ovine prolactin increased Ntcp mRNA 10-fold compared with solvent-treated controls, consistent with the 2-fold increase in Vmax, for Na+/taurocholate co-transport in isolated hepatocytes. These data are the first to demonstrate endogenous physiological regulation by prolactin of Ntcp mRNA in parallel with Na+/taurocholate co-transport activity.
我们已经表明，在怀孕期间，Na⁺/牛磺胆酸盐共转运活性降低，但产后相对于未怀孕的对照组会反弹，并且用绵羊催乳素治疗可增加该活性[甘古利、海德和沃雷（1993年）《药理学与实验治疗学杂志》267卷，82 - 87页]。为了确定这些效应的基础，在纯化的基底外侧肝质膜（bLPM）囊泡中测定了Na⁺/牛磺胆酸盐共转运，并与未怀孕的对照组、怀孕大鼠（怀孕19 - 20天）、产后大鼠（产后48小时）以及用溴隐亭治疗以抑制催乳素分泌的产后大鼠中编码Na⁺/牛磺胆酸盐共转运多肽（Ntcp）的稳态mRNA水平进行了比较。bLPM中Na⁺/牛磺胆酸盐共转运活性（每毫克蛋白质每5秒的纳摩尔数）从未怀孕对照组的10.4±1.8降至怀孕大鼠bLPM中的7.9±0.6，但产后反弹至17.5±1.3；用溴隐亭治疗产后大鼠以抑制催乳素分泌使活性降至14.1±0.9。Northern印迹和狭缝印迹分析显示Ntcp的mRNA有类似变化，因此在Na⁺/牛磺胆酸盐共转运活性与Ntcp mRNA之间观察到正相关。此外，与溶剂处理的对照组相比，用绵羊催乳素治疗去卵巢大鼠使Ntcp mRNA增加了10倍，这与分离的肝细胞中Na⁺/牛磺胆酸盐共转运的Vmax增加2倍一致。这些数据首次证明了催乳素对Ntcp mRNA的内源性生理调节与Na⁺/牛磺胆酸盐共转运活性并行。
