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Nuclear-receptor–mediated regulation of drug– and bile-acid–transporter proteins in gut and liver
Staudinger, Jeffrey Leonard Woody, Sarah K. Sun, Mengxi Cui, Wenqi
Staudinger, Jeffrey Leonard
Woody, Sarah K.
Sun, Mengxi
Cui, Wenqi
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Abstract
Adverse drug events (ADEs) are a common cause of patient morbidity and mortality and are classically thought to result, in part, from variation in expression and activity of hepatic enzymes of drug metabolism. It is now known that alterations in the expression of genes that encode drug- and bile-acid–transporter proteins in both the gut and liver play a previously unrecognized role in determining patient drug response and eventual clinical outcome. Four nuclear receptor (NR) superfamily members, including pregnane X receptor (PXR, NR1I2), constitutive androstane receptor (NR1I3), farnesoid X receptor (NR1H4), and vitamin D receptor (NR1I1), play pivotal roles in drug- and bile-acid– activated programs of gene expression to coordinately regulate drug- and bile-acid transport activity in the intestine and liver. This review focuses on the NR-mediated gene activation of drug and bile-acid transporters in these tissues as well as the possible underlying molecular mechanisms.
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This is an Accepted Manuscript of an article published by Taylor & Francis in Drug Metabolism Reviews on 2015 Sep 2, available online: http://www.tandfonline.com/10.3109/03602532.2012.748793.
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2013-02
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Taylor & Francis
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Staudinger_2013.pdf
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Pregnane x receptor, Constitutive androstane receptor, Farnesoid x receptor, Vitamin D receptor, Cholestasis, Inflammation, Liver disease, Adverse drug events, Drug interactions
Citation
Staudinger, J. L., Woody, S., Sun, M., & Cui, W. (2013). Nuclear-receptor–mediated regulation of drug– and bile-acid–transporter proteins in gut and liver. Drug Metabolism Reviews, 45(1), 48–59. http://doi.org/10.3109/03602532.2012.748793