QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hitzl, M. Articles by Fromm, M. F. Search for Related Content PubMed PubMed Citation Articles by Hitzl, M. Articles by Fromm, M. F.

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Influence of Omeprazole on Multidrug Resistance Protein 3 Expression in Human Liver

Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany (M.H., K.K., U.M.Z., M.F.F.); Department of Pathology, Robert-Bosch-Hospital, Stuttgart, Germany (P.F.); Department of Surgery, Charité, Campus Virchow-Clinic, Humboldt University, Berlin, Germany (A.K.N., P.N.); and Institute of Experimental an Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Erlangen, Germany (M.F.F.)

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 -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 and P < 0.05), in HepG2 cells treated with omeprazole. Finally, MRP3 was induced in HepG2 cells by -naphthoflavone. In summary, treatment with omeprazole and -naphthoflavone is a determinant of variable human hepatic MRP3 expression.

Address correspondence to: Dr. Martin F. Fromm, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Auerbachstr. 112, 70376 Stuttgart, Germany. E-mail: martin.fromm{at}ikp-stuttgart.de

This article has been cited by other articles:

				W. Chen, S.-Y. Cai, S. Xu, L. A. Denson, C. J. Soroka, and J. L. Boyer Nuclear receptors RXR{alpha}:RAR{alpha} are repressors for human MRP3 expression Am J Physiol Gastrointest Liver Physiol, May 1, 2007; 292(5): G1221 - G1227. [Abstract] [Full Text] [PDF]

				J. M. Maher, X. Cheng, A. L. Slitt, M. Z. Dieter, and C. D. Klaassen INDUCTION OF THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN FAMILY OF TRANSPORTERS BY CHEMICAL ACTIVATORS OF RECEPTOR-MEDIATED PATHWAYS IN MOUSE LIVER Drug Metab. Dispos., July 1, 2005; 33(7): 956 - 962. [Abstract] [Full Text] [PDF]

				P. Breedveld, N. Zelcer, D. Pluim, O. Sonmezer, M. M. Tibben, J. H. Beijnen, A. H. Schinkel, O. van Tellingen, P. Borst, and J. H. M. Schellens Mechanism of the Pharmacokinetic Interaction between Methotrexate and Benzimidazoles: Potential Role for Breast Cancer Resistance Protein in Clinical Drug-Drug Interactions Cancer Res., August 15, 2004; 64(16): 5804 - 5811. [Abstract] [Full Text] [PDF]