OSTα-OSTβ:: A major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia

The cellular and subcellular localization and mechanism of transport of the heteromeric organic solute transporter (OST) OST alpha-OST beta was examined in human and rodent epithelia. The two subunits of the transporter were expressed together in human small intestine, kidney, and liver, tissues that also express the apical sodium-dependent bile acid uptake transporter ASBT (SLC10A2). Indirect immunofluorescence microscopy localized OST alpha and OST beta to the basolateral membrane of mouse, rat, and human ileal enterocytes, renal proximal tubular cells, and cholangiocytes. Transport in OST alpha-OSTA beta expressing Xenopus laevis oocytes was unaffected by depletion of intracellular adenosine triphosphate, or by changes in transmembrane Na+, K+, H+, or Cl- concentration gradients. However, the oocytes demonstrated robust substrate efflux and trans-stimulation, indicating that transport occurs by facilitated diffusion. Madin Darby canine kidney cells coexpressing mouse Ost alpha and Ost beta exhibited enhanced apical to basolateral transport of the major glycine and taurine conjugated bile acid species. In conclusion, the selective localization of OST alpha and OST beta to the basolateral plasma membrane of epithelial cells responsible for bile acid and sterol reabsorption, the substrate selectivity of the transporter, and the facilitated diffusion transport mode collectively indicate that OST alpha-OST beta is a key basolateral transporter for the reabsorption of these important steroid-derived molecules. Supplementary material for this article can be found on the HEPATOLOGY website (http://` nterscience.wiley.com/J pagesl 0270-91391suppmatlindex.html).