Abstract
Multidrug resistance protein (MRP) 3 transports bile salts and conjugated xenobiotics from cells (hepatocytes and enterocytes) into the blood. Hepatic MRP3 expression is low under normal conditions but is markedly up-regulated during cholestasis. Since little is known about additional factors increasing human hepatic MRP3 expression, we investigated the variability of MRP3 expression in a large collection of human livers and factors contributing to variable MRP3 expression in liver and HepG2 cells. MRP3 was measured in 62 human livers from patients with and without omeprazole treatment and in HepG2 cells with and without omeprazole or β-naphthoflavone treatment. Livers of patients treated with omeprazole showed 4.8-fold (P< 0.0001) higher MRP3 protein expression compared with the remainder of the population. Accordingly, MRP3 mRNA and protein were induced 2.4- and 1.8-fold, respectively (P < 0.01 andP < 0.05), in HepG2 cells treated with omeprazole. Finally, MRP3 was induced in HepG2 cells by β-naphthoflavone. In summary, treatment with omeprazole and β-naphthoflavone is a determinant of variable human hepatic MRP3 expression.
Footnotes
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Supported by the Deutsche Forschungsgemeinschaft (Bonn, FR 1298/2-1), Grant 01 GG 9846 from the German Federal Ministry of Education and Science, and the Robert Bosch Foundation (Stuttgart, Germany).
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DOI: 10.1124/jpet.102.043547
- Abbreviations:
- HIV
- human immunodeficiency virus
- MRP
- multidrug resistance protein
- PCR
- polymerase chain reaction
- TBS
- Tris-buffered saline
- TBS-T
- Tris-buffered saline/Tween 20
- DMSO
- dimethyl sulfoxide
- RT-PCR
- reverse transcription polymerase chain reaction
- a.u.
- arbitrary units
- Received August 27, 2002.
- Accepted October 3, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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