LIVER DISEASES

Dietrich KEPPLER

Dig Dis. 2017;35:197-202. Progress in the molecular characterization of hepatobiliary transporters. Keppler D. PubMed

Drug Metab Dispos. 2014;42:561-5. The roles of MRP2, MRP3, OATP1B1, and OATP1B3 in conjugated hyperbilirubinemia. Keppler D. PubMed

Clin Pharmacol Ther. 2013;94:95-112. In vitro methods to support transporter evaluation in drug discovery and development. Brouwer KL, Keppler D, Hoffmaster KA, Bow DA, Cheng Y, Lai Y, Palm JE, Stieger B, Evers R; International Transporter Consortium. PubMed

Clin Pharmacol Ther. 2013;94:52-63. Emerging transporters of clinical importance: an update from the International Transporter Consortium. Hillgren KM, Keppler D, Zur AA, Giacomini KM, Stieger B, Cass CE, Zhang L; International Transporter Consortium. PubMed

Handb Exp Pharmacol. 2011;201:299-323. Multidrug resistance proteins (MRPs, ABCCs): importance for pathophysiology and drug therapy. Keppler D. PubMed

Drug Metab Dispos. 2010;38:1054-63. Vectorial transport of nucleoside analogs from the apical to the basolateral membrane in double-transfected cells expressing the human concentrative nucleoside transporter hCNT3 and the export pump ABCC4. Rius M, Keller D, Brom M, Hummel-Eisenbeiss J, Lyko F, Keppler D. PubMed

Nat Rev Drug Discov. 2010;9:215-36. Membrane transporters in drug development. International Transporter Consortium, Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, Chu X, Dahlin A, Evers R, Fischer V, Hillgren KM, Hoffmaster KA, Ishikawa T, Keppler D, Kim RB, Lee CA, Niemi M, Polli JW, Sugiyama Y, Swaan PW, Ware JA, Wright SH, Yee SW, Zamek-Gliszczynski MJ, Zhang L. PubMed

Hepatology. 2009;50:1227-40. Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Nies AT, Koepsell H, Winter S, Burk O, Klein K, Kerb R, Zanger UM, Keppler D, Schwab M, Schaeffeler E. PubMed

Mol Cancer Ther. 2009;8:225-31. Human concentrative nucleoside transporter 1-mediated uptake of 5-azacytidine enhances DNA demethylation. Rius M, Stresemann C, Keller D, Brom M, Schirrmacher E, Keppler D, Lyko F. PubMed

Expert Opin Drug Metab Toxicol. 2008;4:545-68. Interplay of conjugating enzymes with OATP uptake transporters and ABCC/MRP efflux pumps in the elimination of drugs. Nies AT, Schwab M, Keppler D. PubMed

Naunyn Schmiedebergs Arch Pharmacol. 2008;376:449-61. Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). Nies AT, Herrmann E, Brom M, Keppler D. PubMed

J Pharmacol Exp Ther. 2008;324:86-94. ATP-dependent transport of leukotrienes B4 and C4 by the multidrug resistance protein ABCC4 (MRP4). Rius M, Hummel-Eisenbeiss J, Keppler D. PubMed

Drug Metab Dispos. 2007;35:1476-81. Data-based mathematical modeling of vectorial transport across double-transfected polarized cells. Bartholomé K, Rius M, Letschert K, Keller D, Timmer J, Keppler D. PubMed

Toxicol Sci. 2007;97:407-16. Involvement of mitogen-activated protein kinase signaling pathways in microcystin-LR-induced apoptosis after its selective uptake mediated by OATP1B1 and OATP1B3. Komatsu M, Furukawa T, Ikeda R, Takumi S, Nong Q, Aoyama K, Akiyama S, Keppler D, Takeuchi T. PubMed

Pflugers Arch. 2007;453:643-59. The apical conjugate efflux pump ABCC2 (MRP2). PubMed

J Pharmacol Exp Ther. 2006;318:395-402. Vectorial transport of enalapril by Oatp1a1/Mrp2 and OATP1B1 and OATP1B3/MRP2 in rat and human livers. Liu L, Cui Y, Chung AY, Shitara Y, Sugiyama Y, Keppler D, Pang KS. PubMed

Toxicol Sci. 2006;91:140-9.  Molecular characterization and inhibition of amanitin uptake into human hepatocytes. Letschert K, Faulstich H, Keller D, Keppler D. PubMed

Methods Enzymol. 2005;400:531-42. Uptake and efflux transporters for conjugates in human hepatocytes. Keppler D. PubMed

Am J Physiol Gastrointest Liver Physiol. 2006;290:G640-9. Substrate specificity of human ABCC4 (MRP4)-mediated cotransport of bile acids and reduced glutathione. Rius M, Hummel-Eisenbeiss J, Hofmann AF, Keppler D. PubMed

Mol Pharmacol. 2005;68:1031-8. Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells. Kopplow K, Letschert K, König J, Walter B, Keppler D. PubMed

Hepatology. 2005;41:1160-72. Expression and localization of hepatobiliary transport proteins in progressive familial intrahepatic cholestasis. Keitel V, Burdelski M, Warskulat U, Kühlkamp T, Keppler D, Häussinger D, Kubitz R. PubMed

J Pharmacol Exp Ther. 2005;313:549-56. Vectorial transport of the peptide CCK-8 by double-transfected MDCKII cells stably expressing the organic anion transporter OATP1B3 (OATP8) and the export pump ABCC2. Letschert K, Komatsu M, Hummel-Eisenbeiss J, Keppler D. PubMed

Pharmacogenetics. 2004;14:441-52. Mutations in the SLCO1B3 gene affecting the substrate specificity of the hepatocellular uptake transporter OATP1B3 (OATP8). Letschert K, Keppler D, König J. PubMed

Pharmacogenetics. 2004;14:213-23. Identification and functional characterization of the natural variant MRP3-Arg1297His of human multidrug resistance protein 3 (MRP3/ABCC3). Lee YM, Cui Y, König J, Risch A, Jäger B, Drings P, Bartsch H, Keppler D, Nies AT. PubMed

J Hepatol. 2003;39:693-702. Changes in the expression and localization of hepatocellular transporters and radixin in primary biliary cirrhosis. Kojima H, Nies AT, König J, Hagmann W, Spring H, Uemura M, Fukui H, Keppler D. PubMed

Naunyn Schmiedebergs Arch Pharmacol. 2003;368:415-20. Characterization of the transport of the bicyclic peptide phalloidin by human hepatic transport proteins.Fehrenbach T1, Cui Y, Faulstich H, Keppler D. PubMed

Hepatology. 2003;38:374-84. Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Rius M, Nies AT, Hummel-Eisenbeiss J, Jedlitschky G, Keppler D. PubMed

Lab Invest. 2003;83:527-38. Detection of the human organic anion transporters SLC21A6 (OATP2) and SLC21A8 (OATP8) in liver and hepatocellular carcinoma. Cui Y, König J, Nies AT, Pfannschmidt M, Hergt M, Franke WW, Alt W, Moll R, Keppler D. PubMed

Am J Physiol Gastrointest Liver Physiol. 2003;284:G165-74. A common Dubin-Johnson syndrome mutation impairs protein maturation and transport activity of MRP2 (ABCC2). Keitel V, Nies AT, Brom M, Hummel-Eisenbeiss J, Spring H, Keppler D. PubMed

Biol Chem. 2002;383:1001-9. Reconstitution of transport-active multidrug resistance protein 2 (MRP2; ABCC2) in proteoliposomes. Hagmann W, Schubert J, König J, Keppler D. PubMed

J Biol Chem. 2002;277:43058-63. A naturally occurring mutation in the SLC21A6 gene causing impaired membrane localization of the hepatocyte uptake transporter. Michalski C, Cui Y, Nies AT, Nuessler AK, Neuhaus P, Zanger UM, Klein K, Eichelbaum M, Keppler D, Konig J. PubMed

Biochem Pharmacol. 2002;64:151-8. Inhibition of transport across the hepatocyte canalicular membrane by the antibiotic fusidate. Bode KA, Donner MG, Leier I, Keppler D. PubMed

Nat Genet. 2002;31:320-5. Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes. Kikuchi S, Hata M, Fukumoto K, Yamane Y, Matsui T, Tamura A, Yonemura S, Yamagishi H, Keppler D, Tsukita S, Tsukita S. PubMed

Gastroenterology. 2002;122:1545-6; author reply 1546. The human hepatocyte-specific organic anion transporter encoded by the SLC21A8 gene. Keppler D, König J, Cui Y. PubMed

Eur J Biochem. 2002;269:1866-76. Structural requirements for the apical sorting of human multidrug resistance protein 2 (ABCC2). Nies AT, König J, Cui Y, Brom M, Spring H, Keppler D. PubMed

Int J Cancer. 2001;94:492-9. Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma. Nies AT, König J, Pfannschmidt M, Klar E, Hofmann WJ, Keppler D. PubMed

Gastroenterology. 2001;121:1203-8. Expression and localization of the multidrug resistance proteins MRP2 and MRP3 in human gallbladder epithelia. Rost D, König J, Weiss G, Klar E, Stremmel W, Keppler D. PubMed

Mol Pharmacol. 2001;60:934-43. Vectorial transport by double-transfected cells expressing the human uptake transporter SLC21A8 and the apical export pump ABCC2. Cui Y, König J, Keppler D. PubMed

Hepatology. 2001;34:351-9. Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liver. Donner MG, Keppler D. PubMed

Hepatology. 2001;33:1206-16. Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver. Beuers U, Bilzer M, Chittattu A, Kullak-Ublick GA, Keppler D, Paumgartner G, Dombrowski F. PubMed

J Biol Chem. 2001;276:9626-30. Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6. Cui Y, König J, Leier I, Buchholz U, Keppler D. PubMed

Hepatology. 2000;32:1317-28. Impaired protein maturation of the conjugate export pump multidrug resistance protein 2 as a consequence of a deletion mutation in Dubin-Johnson syndrome. Keitel V, Kartenbeck J, Nies AT, Spring H, Brom M, Keppler D. PubMed

Semin Liver Dis. 2000;20:265-72. Hepatic secretion of conjugated drugs and endogenous substances. Keppler D, König J. PubMed

Adv Enzyme Regul. 2000;40:339-49. Localization, substrate specificity, and drug resistance conferred by conjugate export pumps of the MRP family. Keppler D, Kamisako T, Leier I, Cui Y, Nies AT, Tsujii H, König J. PubMed

Am J Physiol Gastrointest Liver Physiol. 2000;278:G522-31. MRP2, a human conjugate export pump, is present and transports fluo 3 into apical vacuoles of Hep G2 cells. Cantz T, Nies AT, Brom M, Hofmann AF, Keppler D. PubMed

Eur J Biochem. 2000;267:1347-58. Characterization of the 5'-flanking region of the human multidrug resistance protein 2 (MRP2) gene and its regulation in comparison withthe multidrug resistance protein 3 (MRP3) gene. Stöckel B, König J, Nies AT, Cui Y, Brom M, Keppler D. PubMed

Am J Physiol Gastrointest Liver Physiol. 2000;278:G156-64. A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane. König J, Cui Y, Nies AT, Keppler D. PubMed

Biochim Biophys Acta. 1999;1461:377-94. Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance. König J, Nies AT, Cui Y, Leier I, Keppler D. PubMed

Free Radic Biol Med. 1999;27:985-91. Export pumps for glutathione S-conjugates. Keppler D. PubMed

Eur J Biochem. 1999;265:281-9. Purification of the human apical conjugate export pump MRP2 reconstitution and functional characterization as substrate-stimulated ATPase. Hagmann W, Nies AT, König J, Frey M, Zentgraf H, Keppler D. PubMed

Adv Enzyme Regul. 1999;39:237-46. Export pumps for anionic conjugates encoded by MRP genes. Keppler D, Cui Y, König J, Leier I, Nies A. PubMed

Gastroenterology. 1999;117:653-60. Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome. Tsujii H, König J, Rost D, Stöckel B, Leuschner U, Keppler D. PubMed

Hepatology. 1999;30:485-90. Transport of monoglucuronosyl and bisglucuronosyl bilirubin by recombinant human and rat multidrug resistance protein 2. Kamisako T, Leier I, Cui Y, König J, Buchholz U, Hummel-Eisenbeiss J, Keppler D. PubMed

Hepatology. 1999;29:1156-63. Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane. König J, Rost D, Cui Y, Keppler D. PubMed

…..

Adv Enzyme Regul. 1990;30:231-42. IMAGING. In vivo metabolism and UTP-depleting action of 2-deoxy-2-fluoro-D-galactose. Grün BR, Berger U, Oberdorfer F, Hull WE, Ostertag H, Keppler D. PubMed