PT - JOURNAL ARTICLE AU - Monika Hitzl AU - Kathrin Klein AU - Ulrich M. Zanger AU - Peter Fritz AU - Andreas K. Nüssler AU - Peter Neuhaus AU - Martin F. Fromm TI - Influence of Omeprazole on Multidrug Resistance Protein 3 Expression in Human Liver AID - 10.1124/jpet.102.043547 DP - 2003 Feb 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 524--530 VI - 304 IP - 2 4099 - http://jpet.aspetjournals.org/content/304/2/524.short 4100 - http://jpet.aspetjournals.org/content/304/2/524.full SO - J Pharmacol Exp Ther2003 Feb 01; 304 AB - 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. The American Society for Pharmacology and Experimental Therapeutics