Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter
Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter
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DOI：
10.1152/ajpgi.1998.274.1.g157
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发表时间：
1998-01-01
影响因子：
4.5
通讯作者：
Dawson, PA
中科院分区：
文献类型：
--
作者：
Craddock, AL;Love, MW;Dawson, PA
胆汁酸的肠肝循环由 Na+ 依赖性转运机制维持。为了更好地理解这些过程，使用 cDNA 末端快速扩增和基因组克隆技术鉴定了全长人回肠 Na+-胆汁酸协同转运蛋白 cDNA。使用 Northern blot 分析确定其组织表达，我们很容易检测到回肠末端和肾脏中的回肠 Na+-胆汁酸协同转运蛋白 mRNA。转录起始位点的直接克隆和作图证实肾脏 cDNA 与回肠 Na+-胆汁酸协同转运蛋白相同。在瞬时转染的 COS 细胞中，回肠 Na+-胆汁酸协同转运蛋白介导的牛磺胆酸盐摄取严格依赖 Na+，不依赖氯。对转染的 COS 或 CHO 细胞中底物特异性的分析表明，缀合和未缀合的胆汁酸均被有效转运。当确定其他潜在底物（例如 3-硫酸雌酮）的抑制常数时，回肠 Na+-胆汁酸协同转运蛋白表现出比相关肝脏 Na+-胆汁酸协同转运蛋白更窄的底物特异性。虽然多特异性肝脏 Na+-胆汁酸协同转运蛋白可能参与肝脏清除有机阴离子代谢物和异生物质，但回肠和肾脏 Na+-胆汁酸协同转运蛋白保留了胆汁酸回收的狭窄特异性。
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.