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.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
| Volume | 274 |
| Issue number | 1 37-1 |
| State | Published - Jan 1998 |
| Externally published | Yes |
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Keywords
- Bile acids
- Hepatic transport
- Ileal transport
- Sulfated bile acids
- Taurocholate
- Ursodeoxycholate
ASJC Scopus subject areas
- Gastroenterology
- Physiology
- Physiology (medical)
Cite this
Expression and transport properties of the human ileal and renal sodium- dependent bile acid transporter. / Craddock, Ann L.; Love, Martha W.; Daniel, Rebecca W.; Kirby, Lyndon C.; Walters, Holly C.; Wong, Melissa; Dawson, Paul A.
In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 274, No. 1 37-1, 01.1998.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression and transport properties of the human ileal and renal sodium- dependent bile acid transporter
AU - Craddock, Ann L.
AU - Love, Martha W.
AU - Daniel, Rebecca W.
AU - Kirby, Lyndon C.
AU - Walters, Holly C.
AU - Wong, Melissa
AU - Dawson, Paul A.
PY - 1998/1
Y1 - 1998/1
N2 - 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.
AB - 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.
KW - Bile acids
KW - Hepatic transport
KW - Ileal transport
KW - Sulfated bile acids
KW - Taurocholate
KW - Ursodeoxycholate
UR - http://www.scopus.com/inward/record.url?scp=0031916146&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031916146&partnerID=8YFLogxK
M3 - Article
C2 - 9458785
AN - SCOPUS:0031916146
VL - 274
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 1 37-1
ER -