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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
PXR: a xenobiotic receptor of diverse function implicated in pharmacogenetics
Bin Zhang1, Wen Xie, Matthew D Krasowski
1Center for Pharmacogenetics, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Abstract:
The pregnane X receptor (PXR; NR1I2), a member of the nuclear receptor superfamily, regulates the expression of drug-metabolic enzymes and transporters involved in the responses of mammals to their chemical environment. The same enzyme and transporter systems are also involved in the homeostasis of numerous endogenous chemicals. The regulatory function of PXR is implicated in normal physiology and diseases, such as drug-drug interactions, hepatic steatosis, vitamin D homeostasis, bile acids homeostasis, steroid hormones homeostasis and inflammatory bowel diseases. As such, any genetic variations of this receptor could potentially have widespread effects on the disposition of xenobiotics and endobiotics. Knowledge concerning the genetic polymorphisms of PXR may help to understand the variations in human drug response and ensure safe drug use. The correlation of PXR genetic polymorphisms with several disease conditions also suggests that this receptor may represent a valid therapeutic for hepato-intestinal disorders such as inflammatory bowel disease and primary sclerosing cholangitis.
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