Adaptive regulation of hepatic bile salt transport: Role of bile salt hydrophobicity and microtubule-dependent vesicular pathway

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.