Dexamethasone modulation of multidrug transporters in normal tissues

FEBS Lett. 1999 Jan 15;442(2-3):208-14. doi: 10.1016/s0014-5793(98)01663-9.

Abstract

The expression of P-glycoprotein (P-gp) and canalicular multispecific organic anion transporter (cMOAT or Mrp2) was evaluated by Western blotting analysis of rat tissues isolated following daily administration (1 mg kg(-1) day(-1)) of dexamethasone over 4 days. Dexamethasone rapidly increased P-gp expression more than 4.5- and 2-fold in liver and lung, respectively, while it was decreased 40% in kidney. cMOAT expression was increased 2-fold in liver and kidney following dexamethasone treatment. The levels of both proteins returned to control values by 6 days after the conclusion of dexamethasone administration. These results indicate that dexamethasone can modulate P-gp and cMOAT expression in specific rat tissues and may have significant relevance for patients treated with dexamethasone as a single agent or in combination therapy with other drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / immunology
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Anion Transport Proteins
  • Blotting, Western
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism*
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacology*
  • Drug Resistance, Multiple
  • Gene Expression / drug effects*
  • Kidney / drug effects
  • Kidney / enzymology
  • Kidney / metabolism
  • Liver / drug effects
  • Liver / enzymology
  • Liver / metabolism
  • Lung / drug effects
  • Lung / enzymology
  • Lung / metabolism
  • Male
  • Membranes / enzymology
  • Molecular Weight
  • Protein Isoforms / immunology
  • Protein Isoforms / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anion Transport Proteins
  • Carrier Proteins
  • Protein Isoforms
  • Dexamethasone