EXPRESSION AND TRANSPORT-PROPERTIES OF THE HUMAN ILEAL AND RENAL SODIUM-DEPENDENT BILE-ACID TRANSPORTER

The enterohepatic circulation of bile acids is maintained by Na+-depen dent transport mechanisms. To better understand these processes, a ful l-length human ileal Na+-bile acid cotransporter cDNA was identified u sing rapid amplification of cDNA ends and genomic cloning techniques. Using Northern blot analysis to determine its tissue expression, we re adily detected the ileal Na+-bile acid cotransporter mRNA in terminal ileum and kidney. Direct cloning and mapping of the transcriptional st art sites confirmed that the kidney cDNA was identical to the ileal Na +-bile acid cotransporter. In transiently transfected COS cells, ileal Na+-bile acid cotransporter-mediated taurocholate uptake was strictly Na+ dependent and chloride independent. Analysis of the substrate spe cificity in transfected COS or CHO cells showed that both conjugated a nd unconjugated bile acids are efficiently transported. When the inhib ition constants for other potential substrates such as estrone-3-sulfa te were determined, the ileal Na+-bile acid cotransporter exhibited a narrower substrate specificity than the related liver Na+-bile acid co transporter. Whereas the multispecific liver Na+-bile acid cotransport er may participate in hepatic clearance of organic anion metabolites a nd xenobiotics, the ileal and renal Na+-bile acid cotransporter retain s a narrow specificity for reclamation of bile acids.