Baumgartner U, Baier P, Schöffel U, Farthmann E H
Department of Surgery, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.
Biochim Biophys Acta. 2001 Jun 20;1539(3):218-24. doi: 10.1016/s0167-4889(01)00108-2.
Indirect evidence for a microtubule-dependent vesicular hepatocellular transport of bile acids has accumulated. Since inhibition of this transport by colchicine can be achieved only at high but not at low bile acid infusion rates we were wondering whether this transport pathway shows a hepatic zonation or not. To answer this question we perfused isolated rat livers antegradely or retrogradely, respectively, with unlabeled and labeled taurocholate or taurodeoxycholate. Inhibition of microtubule-dependent bile acid transport was aimed at co-infusion of colchicine. Periportal cells eliminated the likewise hydrophobic taurodeoxycholate as fast as the more hydrophilic taurocholate. In contrast, pericentral cells excreted taurodeoxycholate much slower than taurocholate. Colchicine did not change the biliary taurocholate excretion profile in periportal and pericentral cells. However, colchicine reduced significantly taurodeoxycholate excretion in pericentral but not in periportal cells. It is concluded that a microtubule-dependent vesicular, colchicine-sensitive transport pathway seems to be involved in the translocation of taurodeoxycholate in pericentral but not in periportal cells. Since such a vesicular bile acid transport is regarded to be much slower than transcellular transport by diffusion, this observation may explain the much slower excretion of hydrophobic bile acids like taurodeoxycholate in pericentral than in periportal cells under physiological conditions.
关于胆汁酸依赖微管的肝细胞囊泡转运的间接证据已经积累起来。由于秋水仙碱对这种转运的抑制仅在高胆汁酸输注速率下而非低速率下才能实现，我们不禁要问这种转运途径是否存在肝小叶分区。为了回答这个问题，我们分别向离体大鼠肝脏进行顺行或逆行灌注，灌注液中含有未标记和标记的牛磺胆酸盐或牛磺脱氧胆酸盐。抑制依赖微管的胆汁酸转运的方法是同时输注秋水仙碱。汇管区细胞清除同样疏水的牛磺脱氧胆酸盐的速度与清除亲水性更强的牛磺胆酸盐的速度一样快。相比之下，中央静脉周围细胞排泄牛磺脱氧胆酸盐的速度比排泄牛磺胆酸盐的速度慢得多。秋水仙碱并没有改变汇管区和中央静脉周围细胞中牛磺胆酸盐的胆汁排泄情况。然而，秋水仙碱显著降低了中央静脉周围细胞中牛磺脱氧胆酸盐的排泄，但对汇管区细胞没有影响。可以得出结论，一种依赖微管的、对秋水仙碱敏感的囊泡转运途径似乎参与了中央静脉周围细胞而非汇管区细胞中牛磺脱氧胆酸盐的转运。由于这种囊泡胆汁酸转运被认为比通过扩散的跨细胞转运要慢得多，这一观察结果可能解释了在生理条件下，像牛磺脱氧胆酸盐这样的疏水性胆汁酸在中央静脉周围细胞中的排泄比在汇管区细胞中慢得多的现象。
