Belknap W M, Zimmer-Nechemias L, Suchy F J, Balistreri W F
Children's Hospital Research Foundation, Cincinnati, Ohio 45229.
Pediatr Res. 1988 Apr;23(4):364-7. doi: 10.1203/00006450-198804000-00005.
To further assess bile acid transport by the developing rat liver, we compared the rate of efflux of taurocholate from hepatocytes isolated from suckling and mature rat livers. Cell content of taurocholate (nmol/mg cell protein), after preloading with [14C]-radiolabeled plus cold bile acid (5-100 microM) was similar in both groups. Total taurocholate efflux, estimated by the decrease in cell taurocholate content, was unexpectedly greater from suckling rat hepatocytes. There was a higher bile acid efflux rate over time and a lower final cell content. Efflux from suckling rat hepatocytes was increased after preloading in incubation concentrations of taurocholate which were above the physiologic range of portal blood concentrations. Inasmuch as the bile acid binding protein content is known to be reduced in the cytoplasm of developing rat liver, intracellular taurocholate may exist largely as free ligand and thus be more readily diffusable. We speculate that the in vivo correlation of enhanced efflux is back diffusion of bile acid from the cell into the sinusoid. The effect could, in part, account for the known absence of a lobular gradient for bile acid uptake in suckling rats and, therefore, contribute to the inefficient hepatic transport of bile acid observed in developing rat liver.
为了进一步评估发育中大鼠肝脏的胆汁酸转运情况,我们比较了从哺乳大鼠和成年大鼠肝脏分离的肝细胞中牛磺胆酸盐的流出速率。在两组中,用[14C]放射性标记的加冷胆汁酸(5 - 100微摩尔)预加载后,牛磺胆酸盐的细胞含量(纳摩尔/毫克细胞蛋白)相似。通过细胞牛磺胆酸盐含量的降低来估计的总牛磺胆酸盐流出量,出乎意料地在哺乳大鼠肝细胞中更大。随着时间推移,胆汁酸流出速率更高,最终细胞含量更低。在高于门静脉血浓度生理范围的孵育浓度下预加载后,哺乳大鼠肝细胞的流出增加。由于已知发育中大鼠肝脏细胞质中的胆汁酸结合蛋白含量降低,细胞内牛磺胆酸盐可能主要以游离配体形式存在,因此更容易扩散。我们推测,流出增强的体内相关性是胆汁酸从细胞反向扩散到血窦中。这种效应可能部分解释了哺乳大鼠中已知的胆汁酸摄取不存在小叶梯度的情况,因此有助于解释在发育中大鼠肝脏中观察到的胆汁酸肝转运效率低下的现象。