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Volume 327, Issue 2 p. 189-193
Research letters
Free Access

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

Olivier Fardel

Corresponding Author

Olivier Fardel

INSERM U 49, Unité de recherches Hépatologiques, Hôpital Pontchaillou, 35033 Rennes, France

Correspondence address: O. Fardel, INSERM U 49, Unité de recherches Hépatologiques, Hôpital Pontchaillou, 35033 Rennes, France. Fax. (33) 99 54 01 37.Search for more papers by this author
Valérie Lecureur

Valérie Lecureur

INSERM U 49, Unité de recherches Hépatologiques, Hôpital Pontchaillou, 35033 Rennes, France

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André Guillouzo

André Guillouzo

INSERM U 49, Unité de recherches Hépatologiques, Hôpital Pontchaillou, 35033 Rennes, France

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First published: July 26, 1993
Citations: 59

Abstract

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 hepatoeytes 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, mdrl 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 mdrl gene.