5-aminoimidazole-4-carboxamide-1-beta-ribofuranoside (AICAR) prevents nuclear translocation of constitutive androstane receptor by AMP-activated protein kinase (AMPK) independent manner

J Toxicol Sci. 2010 Aug;35(4):571-6. doi: 10.2131/jts.35.571.


The nuclear receptor superfamily consists of ligand-dependent transcription factors. Among them, constitutive androstane receptor (CAR) plays a key role in the detoxification of xenobiotics, inducing various drug-metabolizing enzymes including human CYP2B6 and its homologues of other species. AMP-activated protein kinase (AMPK) acts as an important energy sensor, being activated by an increased AMP/ATP ratio. CAR is activated by phenobarbital (PB) treatment. It has been recently reported that AMPK is involved in PB-mediated CYP2B induction both in vitro and in vivo. We investigated the relationship between the functions of AMPK and CAR in rat primary hepatocyte. The AMPK-activator 5-aminoimidazole-4-Carboxamide-1-beta-Ribofuranoside (AICAR) unexpectedly repressed PB-induced CYP2B mRNA expression as well as AMPK-inhibitor compound C. In contrast, both the AMPK-activator metformin and the constitutive active form of AMPK enhanced PB-induced PB-responsive enhancer module-driven reporter gene expression. We demonstrated that AICAR prevented nuclear translocation of CAR in an AMPK-independent manner in rat primary hepatocytes. AICAR might be a convenient probe for studying the mechanisms of PB-induced activation, especially nuclear translocation, of CAR in rat primary hepatocytes.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Active Transport, Cell Nucleus
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Cell Nucleus / metabolism*
  • Constitutive Androstane Receptor
  • Phenobarbital / pharmacology
  • Protein Transport
  • Rats
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Ribonucleotides / pharmacology*


  • Constitutive Androstane Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide
  • Phenobarbital