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

被引:294
作者
Craddock, AL [1 ]
Love, MW [1 ]
Daniel, RW [1 ]
Kirby, LC [1 ]
Walters, HC [1 ]
Wong, MH [1 ]
Dawson, PA [1 ]
机构
[1] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Div Gastroenterol, Winston Salem, NC 27157 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 1998年 / 274卷 / 01期
关键词
ileal transport; hepatic transport; bile acids; taurocholate; ursodeoxycholate; sulfated bile acids;
D O I
10.1152/ajpgi.1998.274.1.G157
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:G157 / G169
页数:13
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