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Expression and regulation of the bile acid transporter, OST α ‐OST β in rat and human intestine and liver
Author(s) -
Khan Ansar A.,
Chow Edwin C. Y.,
Porte Robert J.,
Pang K. Sandy,
Groothuis Geny M. M.
Publication year - 2009
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.663
Subject(s) - calcitriol receptor , ileum , farnesoid x receptor , pregnane x receptor , medicine , lithocholic acid , endocrinology , nuclear receptor , bile acid , jejunum , biology , small intestine , glucocorticoid receptor , receptor , glucocorticoid , biochemistry , vitamin d and neurology , gene , transcription factor
The regulation of the OST α and OST β expression was studied in the rat jejunum, ileum, colon and liver and in human ileum and liver by ligands for the farnesoid X receptor (FXR), pregnane X receptor (PXR), vitamin D receptor (VDR) and glucocorticoid receptor (GR) using precision cut tissue slices. The gradient of protein and mRNA expression in segments of the intestine for rOST α and rOST β paralleled that of rASBT. OST α and OST β mRNA expression, quantified by qRT‐PCR, in rat jejunum, ileum, colon and liver, and in human ileum and liver was positively regulated by FXR and GR ligands. In contrast, the VDR ligand, 1,25(OH) 2 D 3 decreased the expression of rOST α ‐rOST β in rat intestine, but had no effect on human ileum, and rat and human liver slices. Lithocholic acid (LCA) decreased the expression of rOST α and rOST β in rat ileum but induced OST α ‐OST β expression in rat liver slices, and human ileum and liver slices. The PXR ligand, pregnenolone‐16 α carbonitrile (PCN) had no effect. This study suggest that, apart from FXR ligands, the OST α and OST β genes are also regulated by VDR and GR ligands and not by PXR ligands. This study show that VDR ligands exerted different effects on OST α ‐OST β in the rat and human intestine and liver compared with other nuclear receptors, FXR, PXR, and GR, pointing to species‐ and organ‐specific differences in the regulation of OST α ‐OST β genes. Copyright © 2009 John Wiley & Sons, Ltd.