Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter.
Article Details
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Craddock AL, Love MW, Daniel RW, Kirby LC, Walters HC, Wong MH, Dawson PA
Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter.
Am J Physiol. 1998 Jan;274(1 Pt 1):G157-69.
- PubMed ID
- 9458785 [ View in PubMed]
- Abstract
The enterohepatic circulation of bile acids is maintained by Na(+)-dependent transport mechanisms. To better understand these processes, a full-length human ileal Na(+)-bile acid cotransporter cDNA was identified using rapid amplification of cDNA ends and genomic cloning techniques. Using Northern blot analysis to determine its tissue expression, we readily detected the ileal Na(+)-bile acid cotransporter mRNA in terminal ileum and kidney. Direct cloning and mapping of the transcriptional start 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 specificity in transfected COS or CHO cells showed that both conjugated and unconjugated bile acids are efficiently transported. When the inhibition constants for other potential substrates such as estrone-3-sulfate were determined, the ileal Na(+)-bile acid cotransporter exhibited a narrower substrate specificity than the related liver Na(+)-bile acid cotransporter. Whereas the multispecific liver Na(+)-bile acid cotransporter may participate in hepatic clearance of organic anion metabolites and xenobiotics, the ileal and renal Na(+)-bile acid cotransporter retains a narrow specificity for reclamation of bile acids.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Cholic Acid Ileal sodium/bile acid cotransporter Protein Humans UnknownSubstrateInhibitorInducerDetails Cyclosporine Ileal sodium/bile acid cotransporter Protein Humans UnknownInhibitorDetails Deoxycholic acid Ileal sodium/bile acid cotransporter Protein Humans UnknownInhibitorDetails Glycochenodeoxycholic Acid Ileal sodium/bile acid cotransporter Protein Humans UnknownSubstrateDetails Taurocholic acid Ileal sodium/bile acid cotransporter Protein Humans UnknownSubstrateInducerDetails Ursodeoxycholic acid Ileal sodium/bile acid cotransporter Protein Humans UnknownInhibitorDetails - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Cyclosporine Ileal sodium/bile acid cotransporter Ki (nM) 24000 N/A N/A Details Deoxycholic acid Ileal sodium/bile acid cotransporter Ki (nM) 6300 N/A N/A Details Ursodeoxycholic acid Ileal sodium/bile acid cotransporter Ki (nM) 75000 N/A N/A Details