Up-regulation of multidrug resistance-associated protein 2 (MRP2) expression in rat hepatocytes by dexamethasone

FEBS Lett. 1999 Oct 15;459(3):381-5. doi: 10.1016/s0014-5793(99)01295-8.


Regulation of multidrug resistance-associated protein (MRP2) expression in response to dexamethasone (DEX) was analyzed using mainly primary rat hepatocytes. Enhanced levels of MRP2 mRNAs associated with increased amounts of a 190 kDa MRP2 were found in cultured DEX-treated hepatocytes; similarly, administration of DEX to rats (100 mg/kg, i.p.) led to a marked increase of hepatic amounts of MRP2 mRNAs. Maximal induction of MRP2 expression in DEX-treated primary hepatocytes was reached with 10(-5) M DEX, a concentration higher than that (10(-7) M) required for maximal up-regulation of tyrosine aminotransferase (TAT), a typical glucocorticoid receptor-regulated enzyme. In addition, the anti-glucocorticoid compound RU486 failed to inhibit MRP2 induction caused by DEX whereas it fully blocked that of TAT. These findings therefore demonstrate that DEX is a potent inducer of MRP2 expression in rat hepatocytes through a mechanism that seems not to involve the classical glucocorticoid receptor pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Dexamethasone / pharmacology*
  • Hormone Antagonists / pharmacology
  • In Vitro Techniques
  • Liver / cytology
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Mifepristone / pharmacology
  • Mitochondrial Proteins*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucocorticoid / metabolism
  • Ribosomal Proteins / drug effects
  • Ribosomal Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Time Factors
  • Up-Regulation


  • Anti-Inflammatory Agents
  • Hormone Antagonists
  • MRP2 protein, S cerevisiae
  • Mitochondrial Proteins
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • Mifepristone
  • Dexamethasone