Dexamethasone modulation of multidrug transporters in normal tissues

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 exp...

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Veröffentlicht in:FEBS letters 1999-01, Vol.442 (2), p.208-214
Hauptverfasser: Demeule, Michel, Jodoin, Julie, Beaulieu, Édith, Brossard, Mathieu, Béliveau, Richard
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creator Demeule, Michel
Jodoin, Julie
Beaulieu, Édith
Brossard, Mathieu
Béliveau, Richard
description 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.
doi_str_mv 10.1016/S0014-5793(98)01663-9
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subjects Animals
Anion Transport Proteins
ATP Binding Cassette Transporter, Subfamily B, Member 1 - immunology
ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism
BBM, brush border membranes
Blotting, Western
Carrier Proteins - immunology
Carrier Proteins - metabolism
cMOAT
Dexamethasone
Dexamethasone - administration & dosage
Dexamethasone - pharmacology
Drug Resistance, Multiple
ECL, enhanced chemiluminescence
Gene Expression - drug effects
IAAP, [125I]iodoaryl azidoprazosin
Kidney - drug effects
Kidney - enzymology
Kidney - metabolism
Liver - drug effects
Liver - enzymology
Liver - metabolism
Lung - drug effects
Lung - enzymology
Lung - metabolism
mAb, monoclonal antibody
Male
Membranes - enzymology
Molecular Weight
Mrp2
P-glycoprotein
P-gp, P-glycoprotein
pAb, polyclonal antibody
Protein expression
Protein Isoforms - immunology
Protein Isoforms - metabolism
PVDF, polyvinylidene difluoride
Rats
Rats, Sprague-Dawley
spgp, sister P-glycoprotein
TBS-T, Tris buffered saline with 0.3% Tween 20
title Dexamethasone modulation of multidrug transporters in normal tissues
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