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Molecular Pharmacology

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Research ArticleArticle

Transactivation of Rat Apical Sodium-Dependent Bile Acid Transporter and Increased Bile Acid Transport by 1α,25-Dihydroxyvitamin D3 via the Vitamin D Receptor

Xianghai Chen, Frank Chen, Shanjun Liu, Hartmut Glaeser, Paul A. Dawson, Alan F. Hofmann, Richard B. Kim, Benjamin L. Shneider and K. Sandy Pang
Molecular Pharmacology June 2006, 69 (6) 1913-1923; DOI: https://doi.org/10.1124/mol.105.020792
Xianghai Chen
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Frank Chen
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Shanjun Liu
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Hartmut Glaeser
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Paul A. Dawson
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Alan F. Hofmann
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Richard B. Kim
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Benjamin L. Shneider
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K. Sandy Pang
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Abstract

Transactivation of the rat apical sodium-dependent bile acid transporter (ASBT; Slc10a2) by 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] via the vitamin D receptor (VDR), was studied. Levels of ASBT protein and mRNA were low in the duodenum and high in the ileum, and both were induced by 1,25(OH)2D3. The nuclear receptor protein, VDR, was present uniformly in the duodenum, jejunum, and ileum of the rat small intestine. The physiological relevance of ASBT induction by 1,25(OH)2D3 was assessed by measuring absorption of cholylsarcosine, a non-metabolized synthetic bile acid analog, from duodenal or ileal closed loops of the perfused rat small intestine preparation. Absorption of cholylsarcosine was much greater from the ileal segment (28-fold that of the duodenum under control conditions) and was enhanced with 1,25(OH)2D3 treatment. Transient transfection analysis of the rat ASBT promoter in Caco-2 cells revealed concentration-dependent enhancement of luciferase reporter activity after treatment with 1,25(OH)2D3. The activation by 1,25(OH)2D3 was abrogated after site-directed mutagenesis or deletion of the vitamin D response element (VDRE) in the ASBT promoter. Gel-shift mobility assays of nuclear extracts from rat ileum showed that both rat retinoid X receptor and VDR were bound to the VDRE. The results indicate that rat ASBT gene expression is activated by 1,25(OH)2D3 by specific binding to the VDRE and that such activation enhances ileal bile acid transport. Human ABST mRNA and promoter activity were also increased in Caco-2 cells treated with 1,25(OH)2D3, suggesting a physiological role of VDR in human ileal bile acid homeostasis.

  • Received November 12, 2005.
  • Accepted February 15, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 69 (6)
Molecular Pharmacology
Vol. 69, Issue 6
1 Jun 2006
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Research ArticleArticle

Transactivation of Rat Apical Sodium-Dependent Bile Acid Transporter and Increased Bile Acid Transport by 1α,25-Dihydroxyvitamin D3 via the Vitamin D Receptor

Xianghai Chen, Frank Chen, Shanjun Liu, Hartmut Glaeser, Paul A. Dawson, Alan F. Hofmann, Richard B. Kim, Benjamin L. Shneider and K. Sandy Pang
Molecular Pharmacology June 1, 2006, 69 (6) 1913-1923; DOI: https://doi.org/10.1124/mol.105.020792

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Research ArticleArticle

Transactivation of Rat Apical Sodium-Dependent Bile Acid Transporter and Increased Bile Acid Transport by 1α,25-Dihydroxyvitamin D3 via the Vitamin D Receptor

Xianghai Chen, Frank Chen, Shanjun Liu, Hartmut Glaeser, Paul A. Dawson, Alan F. Hofmann, Richard B. Kim, Benjamin L. Shneider and K. Sandy Pang
Molecular Pharmacology June 1, 2006, 69 (6) 1913-1923; DOI: https://doi.org/10.1124/mol.105.020792
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