Regulation by dexamethasone of P-glycoprotein expression in cultured rat hepatocytes

FEBS Lett. 1993 Jul 26;327(2):189-93. doi: 10.1016/0014-5793(93)80167-s.


We have examined P-glycoprotein (P-gp) expression and function in cultured rat hepatocytes in response to dexamethasone (DEX), which is known to modulate various liver functions. Northern blot analyses revealed high levels of P-gp mRNAs in cultured untreated liver cells in comparison to those found in freshly isolated hepatocytes, while DEX-treated hepatocytes also displayed elevated, although weaker, P-gp levels. Similarly, Western blotting analysis indicated high levels of P-gp in liver cells maintained in the absence of DEX. The use of mdr gene-specific probes allowed us to show that DEX-modulated P-gp induction in cultured hepatocytes involved mostly, if not specifically, mdr1 gene regulation. Doxorubicin P-gp-mediated efflux analyses revealed lower intracellular doxorubicin accumulation in DEX-untreated liver cells than in DEX-treated cells, thus indicating that over-expressed P-gp was functional. These data clearly show that DEX treatment strongly modulates P-gp expression in primary rat hepatocyte cultures through a specific effect on the mdr1 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Cells, Cultured
  • Dexamethasone / pharmacology*
  • Doxorubicin / metabolism
  • Drug Resistance / genetics
  • Electrophoresis, Polyacrylamide Gel
  • Gene Expression Regulation / drug effects*
  • Immunoblotting
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Verapamil / pharmacology


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Carrier Proteins
  • Membrane Glycoproteins
  • RNA, Messenger
  • Dexamethasone
  • Doxorubicin
  • Verapamil