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

Authors:
  • OFOlivier Fardel
    Olivier Fardel
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Abstract
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.

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