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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Published on: November 15, 2013

Hepatic drug transporters and nuclear receptors: regulation by therapeutic agents

Aldo-D Mottino1, Viviana-A Catania

  • 1Instituto de Fisiologia Experimental, Universidad Nacional de Rosario, Suipacha 570-Rosario, Argentina. amottino@unr.edu.ar

World Journal of Gastroenterology
|December 17, 2008
PubMed

Insights

Liver drug transporters like MDR1, MRP2, and BCRP are regulated by nuclear receptors PXR and CAR. Therapeutic agents modulate these transporters, impacting drug elimination and liver function.

Area of Science:

  • Hepatobiliary science
  • Pharmacology
  • Molecular biology

Background:

  • The canalicular membrane of hepatocytes is crucial for eliminating toxic substances via bile.
  • Major canalicular transporters (MDR1, MRP2, BCRP) mediate the excretion of endo- and xenobiotics.
  • Expression and localization of these transporters are tightly regulated by transcriptional and post-transcriptional mechanisms.

Purpose of the Study:

  • To describe the role of nuclear receptors (NRs) in regulating drug transporter expression in hepatocytes.
  • To highlight the involvement of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) in this process.
  • To provide examples of therapeutic agents that modulate liver drug transporters via PXR and CAR.

Main Methods:

  • Review of transcriptional regulation of major canalicular transporters.
  • Description of the function of Class II nuclear receptors (PXR and CAR).
  • Analysis of therapeutic agent interactions with NRs and drug transporters.

Main Results:

  • Nuclear receptors PXR and CAR are key regulators of multidrug resistance protein expression.
  • Ligand-modulated NRs control transporter expression to meet physiological demands.
  • Specific therapeutic agents activate or inactivate PXR and CAR, altering drug transporter activity.

Conclusions:

  • PXR and CAR play significant roles in modulating the expression of key liver drug transporters.
  • Therapeutic interventions targeting PXR and CAR can influence drug disposition and elimination.
  • Understanding these NR-mediated pathways is vital for managing drug efficacy and toxicity in liver diseases.

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