Demonstration of a transcellular vesicle pathway for biliary excretion of inulin in rat liver.

We tested the hypothesis that the blood to bile transport of hydrophilic inert nonelectrolytes such as inulin is mediated in part by a transcellular pathway involving endosomelike vesicles (transcytosis). Forty minutes after intravenous injection of [3H]methoxyinulin into renal pedicle ligated rats, 0.8% of the radioactivity was recovered in liver homogenate and 85% +/- 3.6% of this radioactivity was associated with membrane bound vesicles. Subcellular fractionation studies and electron microscopy confirmed this association. If rats were treated with taurochenodeoxycholic acid, 5 mumol/100 g body wt, the hepatocellular uptake of [3H]methoxyinulin increased approximately twofold and [3H]methoxyinulin was again recovered in small subcellular vesicles. Furthermore, taurochenodeoxycholic acid also stimulated the biliary excretion of [3H]methoxyinulin, which peaked in bile at 20 min. Taurochenodeoxycholic acid had similar effects on the biliary excretion of horseradish peroxidase, a protein known to be transported from blood to bile by membrane vesicles. Thus under the conditions of these experiments, the dihydroxy bile acid taurochenodeoxycholic acid can stimulate the rate of vesicle-dependent transcellular transport into bile. If inulin clearance represents a maximal estimate of this process, only 6%-8% of total bile production in the rat under basal conditions would be mediated by vesicle-mediated transcytosis.