Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter.

Article Details

Citation

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
DrugTransporterKindOrganismPharmacological ActionActions
Cholic AcidIleal sodium/bile acid cotransporterProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
CyclosporineIleal sodium/bile acid cotransporterProteinHumans
Unknown
Inhibitor
Details
Deoxycholic acidIleal sodium/bile acid cotransporterProteinHumans
Unknown
Inhibitor
Details
Glycochenodeoxycholic AcidIleal sodium/bile acid cotransporterProteinHumans
Unknown
Substrate
Details
Taurocholic acidIleal sodium/bile acid cotransporterProteinHumans
Unknown
Substrate
Inducer
Details
Ursodeoxycholic acidIleal sodium/bile acid cotransporterProteinHumans
Unknown
Inhibitor
Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CyclosporineIleal sodium/bile acid cotransporterKi (nM)24000N/AN/ADetails
Deoxycholic acidIleal sodium/bile acid cotransporterKi (nM)6300N/AN/ADetails
Ursodeoxycholic acidIleal sodium/bile acid cotransporterKi (nM)75000N/AN/ADetails