Adaptive regulation of hepatic bile salt transport: Role of bile salt hydrophobicity and microtubule-dependent vesicular pathway
Adaptive regulation of hepatic bile salt transport: Role of bile salt hydrophobicity and microtubule-dependent vesicular pathway
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DOI：
10.1016/s0168-8278(97)80437-0
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发表时间：
1997-03-01
影响因子：
25.7
通讯作者：
Accatino, L
中科院分区：
文献类型：
--
作者：
Arrese, M;Pizarro, M;Accatino, L
背景/目的：胆汁盐的肝脏转运可以通过胆汁盐池大小和/或胆汁盐通过肝脏的流量的变化来调节，胆汁盐池的长期消耗与最大牛磺胆酸盐转运的下调和小管膜特异性胆汁盐结合位点的减少有关。疏水性；方法：对雄性大鼠进行24小时或48小时外胆道分流诱导胆汁盐库耗竭，观察基础胆汁的情况、胆盐分泌和脂质分泌、三种不同疏水性胆汁盐（牛磺熊去氧胆酸盐、牛磺胆酸盐和牛磺鹅去氧胆酸盐）的最大分泌率以及胆汁盐转运能力的变化。在对照和胆汁盐耗尽的大鼠中测量了微管依赖性囊泡途径的两种标记物（辣根过氧化物酶和聚乙二醇分子量-900）的胆汁排泄，还评估了牛磺胆酸刺激的辣根过氧化物酶胆汁排泄，以确定胆汁盐流经肝细胞的恢复是否增加了胆汁盐耗尽的大鼠中该标记物的排泄，结果：长期胆汁分流后观察到的三种胆汁盐最大分泌率的降低显然与其疏水性有关，与牛磺胆酸盐相比，牛磺鹅去氧胆酸盐的降低幅度较大，牛磺熊去氧胆酸盐的降低幅度较小。结论：胆汁盐库耗尽后，肝胆汁盐最大转运能力下降的幅度与输注胆汁盐的疏水性直接相关，功能性抑制的囊泡转运途径似乎也是造成这种现象的一个因素。
Background/Aims: The hepatic transport of bile salts can be regulated by changes in bile salt pool size and/ or in the flux of bile salts through the liver, Prolonged bile salt pool depletion is associated with down-regulation of maximum taurocholate transport and decreased canalicular membrane specific bile salt binding sites, This study was undertaken to investigate: a) whether adaptive down-regulation of maximum hepatic bile salt transport occurs to the same extent for bile acids of different hydrophobicity; and b) the role of microtubule-dependent vesicular pathway in the adaptive changes of bile salt transport capacity.Methods: Male rats were subjected to 24-h or 48-h external biliary diversion to induce bile salt pool depletion, Basal bile how, bile salt secretion and lipid secretion, maximum secretory rate of three bile salts of different hydrophobicity (tauroursodeoxycholate, taurocholate and taurochenodeoxycholate) and changes in the biliary excretion of two markers of the microtubule-dependent vesicular pathway (horseradish peroxidase and polyethyleneglycol molecular weight-900) were measured in control and bile salt-depleted rats, Taurocholate-stimulated horse-radish peroxidase biliary excretion was also assessed in order to define whether the restoration of bile salt flux across the hepatocytes increased the excretion of this marker in bile salt-depleted rats,Results: The reduction in the maximum secretory rate of the three bile salts under study observed after prolonged biliary diversion was clearly related to their hydrophobicity, with greater reduction for taurochenodeoxycholate and smaller reduction for tauroursodeoxycholate, compared with taurocholate, The biliary excretion of vesicular transport markers was significantly reduced in bile salt-depleted rats, However, when stimulated by taurocholate, biliary excretion of horseradish peroxidase was similar to controls.Conclusions: The magnitude of the decrease of the hepatic bile salt maximum transport capacity seen after bile salt pool depletion is directly related to the hydrophobicity of the bile salt infused, A functionally depressed vesicular transport pathway appears to be also a contributing factor to this phenomenon.