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Bile acid transport and regulating functions in the human biliary epithelium

Whether bile acids regulate biliary epithelial cell (BEC) secretory functions in human is poorly known. The purpose of the study was to determine if human gallbladder‐derived BEC exhibit bile acid transport activity that affect their secretory functions and to evaluate the influence of bile acid hydrophobicity in this response by comparing the effects of tauroursodeoxycholate (TUDC) and of taurochenodeoxycholate (TCDC). Expression of the apical sodium‐dependent bile acid transporter (ASBT) and of the organic anion transporting polypeptide (OATP‐A) was detected and associated with sodium‐dependent and sodium‐independent [3H]taurocholate uptake in BEC. Sodium‐dependent uptake (Km, 66 ± 2.5 μmol/L; Vmax, 39.4 ± 4.6 pmol/mg protein/min) was significantly higher than sodium‐independent uptake. TCDC stimulated Cl− efflux and mucin secretion in cultured cells, and both effects were sodium‐dependent. Both TCDC and TUDC were efficiently transported in BEC, as assessed by competitive uptake experiments. However, as compared with TCDC, TUDC induced significantly lower mucin secretion whereas there was no significant difference between TCDC‐ and TUDC‐induced chloride efflux. Protein kinase C down‐regulation caused a 70% reduction in TUDC‐induced mucin secretion, but did not affect TCDC‐induced secretion, which was mediated predominantly by Ca2+/calmodulin‐dependent protein kinase II activation. These results provide evidence that bile acids may be transported mainly via ASBT in human gallbladder BEC and stimulate hydroelectrolytic and mucin secretion in these cells. Individual bile acids activate different signaling pathways leading to a different balance between mucin and chloride secretion. The differential effect of TUDC may cause a reduction in bile inspissation and provide a benefit in biliary disorders.