D Keppler

Summary

Affiliation: German Cancer Research Center
Country: Germany

Publications

  1. ncbi request reprint A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane
    J Konig
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, D 69120 Heidelberg, Germany
    Am J Physiol Gastrointest Liver Physiol 278:G156-64. 2000
  2. ncbi request reprint Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane
    J Konig
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Hepatology 29:1156-63. 1999
  3. ncbi request reprint Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide
    J Konig
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, D 69120 Heidelberg, Germany
    J Biol Chem 275:23161-8. 2000
  4. ncbi request reprint cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats
    M Buchler
    Deutsches Krebsforschungszentrum, D 69120 Heidelberg, Federal Republic of Germany
    J Biol Chem 271:15091-8. 1996
  5. ncbi request reprint Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma
    A T Nies
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Int J Cancer 94:492-9. 2001
  6. ncbi request reprint Purification of the human apical conjugate export pump MRP2 reconstitution and functional characterization as substrate-stimulated ATPase
    W Hagmann
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Eur J Biochem 265:281-9. 1999
  7. ncbi request reprint Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6
    Y Cui
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, D 69120 Heidelberg, Germany
    J Biol Chem 276:9626-30. 2001
  8. ncbi request reprint ATP-dependent transport of taurocholate across the hepatocyte canalicular membrane mediated by a 110-kDa glycoprotein binding ATP and bile salt
    M Muller
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany
    J Biol Chem 266:18920-6. 1991
  9. ncbi request reprint Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance
    J Konig
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, D 69120, Heidelberg, Germany
    Biochim Biophys Acta 1461:377-94. 1999
  10. ncbi request reprint Impaired protein maturation of the conjugate export pump multidrug resistance protein 2 as a consequence of a deletion mutation in Dubin-Johnson syndrome
    V Keitel
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Hepatology 32:1317-28. 2000

Collaborators

Detail Information

Publications43

  1. ncbi request reprint A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane
    J Konig
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, D 69120 Heidelberg, Germany
    Am J Physiol Gastrointest Liver Physiol 278:G156-64. 2000
    ..Our results indicate that OATP2 is important for the uptake of organic anions, including bilirubin conjugates and sulfobromophthalein, in human liver...
  2. ncbi request reprint Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane
    J Konig
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Hepatology 29:1156-63. 1999
    ..These results indicate that the basolateral MRP isoform, MRP3, may be upregulated when the canalicular secretion of anionic conjugates by MRP2 is impaired...
  3. ncbi request reprint Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide
    J Konig
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, D 69120 Heidelberg, Germany
    J Biol Chem 275:23161-8. 2000
    ..Thus, human OATP8 is a new uptake transporter in the basolateral hepatocyte membrane with an overlapping but distinct substrate specificity as compared with OATP2, which is localized to the same membrane domain...
  4. ncbi request reprint cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats
    M Buchler
    Deutsches Krebsforschungszentrum, D 69120 Heidelberg, Federal Republic of Germany
    J Biol Chem 271:15091-8. 1996
    ..The results identify cMrp as a canalicular transport protein with a novel sequence and with a function similar to the one of the MRP...
  5. ncbi request reprint Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma
    A T Nies
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Int J Cancer 94:492-9. 2001
    ..When MRP1 was detected by immunofluorescence microscopy, it was localized on the intracellular membranes of carcinoma cells. Thus, plasma membrane expression of MRP2 and MRP3, but not of MRP1, can contribute to the MDR phenotype of HCC...
  6. ncbi request reprint Purification of the human apical conjugate export pump MRP2 reconstitution and functional characterization as substrate-stimulated ATPase
    W Hagmann
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Eur J Biochem 265:281-9. 1999
    ....
  7. ncbi request reprint Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6
    Y Cui
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, D 69120 Heidelberg, Germany
    J Biol Chem 276:9626-30. 2001
    ..Human OATP2 may play a key role in the prevention of hyperbilirubinemia by facilitating the selective entry of unconjugated bilirubin and its glucuronate conjugates into human hepatocytes...
  8. ncbi request reprint ATP-dependent transport of taurocholate across the hepatocyte canalicular membrane mediated by a 110-kDa glycoprotein binding ATP and bile salt
    M Muller
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany
    J Biol Chem 266:18920-6. 1991
    ..These results demonstrate that gp110 functions as carrier in the ATP-dependent transport of bile salts from the hepatocyte into bile. This export carrier is distinct from hitherto characterized ATP-dependent transport systems...
  9. ncbi request reprint Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance
    J Konig
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, D 69120, Heidelberg, Germany
    Biochim Biophys Acta 1461:377-94. 1999
    ..Because of its function in the terminal excretion of cytotoxic and carcinogenic substances, MRP2 as well as other members of the MRP family, play an important role in detoxification and chemoprevention...
  10. ncbi request reprint Impaired protein maturation of the conjugate export pump multidrug resistance protein 2 as a consequence of a deletion mutation in Dubin-Johnson syndrome
    V Keitel
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Hepatology 32:1317-28. 2000
    ..This is the first mutation in Dubin-Johnson syndrome shown to cause deficient MRP2 maturation and impaired sorting of this glycoprotein to the apical membrane...
  11. ncbi request reprint ATP-dependent para-aminohippurate transport by apical multidrug resistance protein MRP2
    I Leier
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Kidney Int 57:1636-42. 2000
    ..This ATP-dependent export pump for anionic conjugates and additional amphiphilic anions was cloned recently and localized to the apical membrane of proximal tubules in human and rat kidney...
  12. ncbi request reprint The canalicular multidrug resistance protein, cMRP/MRP2, a novel conjugate export pump expressed in the apical membrane of hepatocytes
    D Keppler
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Adv Enzyme Regul 37:321-33. 1997
    ....
  13. ncbi request reprint ATP-dependent primary active transport of cysteinyl leukotrienes across liver canalicular membrane. Role of the ATP-dependent transport system for glutathione S-conjugates
    T Ishikawa
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany
    J Biol Chem 265:19279-86. 1990
    ..These results demonstrate that the ATP-dependent carrier system is responsible for the transport of cysteinyl leukotrienes and glutathione S-conjugates from the hepatocytes into bile...
  14. ncbi request reprint Changes in the localization of the rat canalicular conjugate export pump Mrp2 in phalloidin-induced cholestasis
    D Rost
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg
    Hepatology 29:814-21. 1999
    ..The resulting cholestasis can therefore be explained in part by the loss of export pumps, including Mrp2, from the canalicular membrane...
  15. ncbi request reprint Absence of the canalicular isoform of the MRP gene-encoded conjugate export pump from the hepatocytes in Dubin-Johnson syndrome
    J Kartenbeck
    Division of Cell Biology, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Hepatology 23:1061-6. 1996
    ....
  16. ncbi request reprint Hepatobiliary elimination of the peroxisome proliferator nafenopin by conjugation and subsequent ATP-dependent transport across the canalicular membrane
    G Jedlitschky
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, F R G
    Biochem Pharmacol 48:1113-20. 1994
    ....
  17. ncbi request reprint Leukotriene uptake by hepatocytes and hepatoma cells
    I Leier
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany
    Eur J Biochem 209:281-9. 1992
    ..Only LTB4, but not cysteinyl leukotrienes, is taken up and metabolized by the transformed hepatoma cells...
  18. ncbi request reprint Vectorial transport by double-transfected cells expressing the human uptake transporter SLC21A8 and the apical export pump ABCC2
    Y Cui
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Mol Pharmacol 60:934-43. 2001
    ..The double-transfected cells provide a useful system for the identification of transport substrates and transport inhibitors including drug candidates...
  19. ncbi request reprint Identification of the biosynthetic leukotriene C4 export pump in murine mastocytoma cells as a homolog of the multidrug-resistance protein
    I Leier
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Eur J Biochem 242:201-5. 1996
    ..7% and 89.7% identical with the corresponding sequences of human MRP. These results indicate that the ATP-dependent release of leukotriene C4 by murine mastocytoma cells is mediated by murine Mrp...
  20. ncbi request reprint Transport and in vivo elimination of cysteinyl leukotrienes
    D Keppler
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany
    Adv Enzyme Regul 32:107-16. 1992
    ..The leukotriene carrier is distinct from other ATP-dependent export carriers identified in this membrane domain, such as the ATP-dependent bile salt export carrier (25) and the multidrug export carrier (27)...
  21. ncbi request reprint The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides
    G Jedlitschky
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, D 69120 Heidelberg, Germany
    J Biol Chem 275:30069-74. 2000
    ..Thus, cyclic nucleotides are physiological substrates for MRP5; moreover, MRP5 may represent a novel pharmacological target for the enhancement of tissue levels of cGMP...
  22. ncbi request reprint Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome
    H Tsujii
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Gastroenterology 117:653-60. 1999
    ..The aim of this study was the elucidation of all exon-intron boundaries of the MRP2 gene as a prerequisite for the analysis of mutations in patients with Dubin-Johnson syndrome...
  23. ncbi request reprint Hepatic secretion of conjugated drugs and endogenous substances
    D Keppler
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Semin Liver Dis 20:265-72. 2000
    ....
  24. ncbi request reprint Inhibition by cyclosporin A of adenosine triphosphate-dependent transport from the hepatocyte into bile
    M Kadmon
    Division of Tumor Biochemistry, Deutsches Krebsforschungzentrum, Heidelberg, Germany
    Gastroenterology 104:1507-14. 1993
    ..Inhibition of ATP-dependent bile salt transport may induce cholestasis...
  25. pmc Selective inhibition of MDR1 P-glycoprotein-mediated transport by the acridone carboxamide derivative GG918
    A Wallstab
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Br J Cancer 79:1053-60. 1999
    ....
  26. ncbi request reprint Metabolism of cysteinyl leukotrienes in monkey and man
    M Huber
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany
    Eur J Biochem 194:309-15. 1990
    ..Moreover, omega-oxidation and subsequent beta-oxidation from the omega-end contribute to the metabolic degradation of LTE4 not only in monkey but also in man...
  27. ncbi request reprint Inhibition of leukotriene omega-oxidation by omega-trifluoro analogs of leukotrienes
    G Jedlitschky
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany
    Arch Biochem Biophys 282:333-9. 1990
    ..omega-Trifluoro analogs of leukotrienes provide a new tool for interfering with the inactivation of leukotrienes in the omega-oxidation pathway...
  28. ncbi request reprint Expression of the MRP2 gene-encoded conjugate export pump in human kidney proximal tubules and in renal cell carcinoma
    T P Schaub
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    J Am Soc Nephrol 10:1159-69. 1999
    ..This conjugate-transporting ATPase encoded by the MRP2 gene has a similar substrate specificity as the multidrug resistance protein MRP1, and may contribute to the multidrug resistance of renal clear-cell carcinomas...
  29. ncbi request reprint w-oxidation products of leukotriene E4 in bile and urine of the monkey
    H A Ball
    Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany
    Biochem Biophys Res Commun 148:664-70. 1987
    ..Time course studies of the [3H]leukotriene metabolite pattern in bile and urine showed that w-hydroxy-leukotriene E4 was decreasing as w-carboxy-leukotriene E4 and additional polar derivatives were increasing...
  30. ncbi request reprint Expression and immunolocalization of the multidrug resistance proteins, MRP1-MRP6 (ABCC1-ABCC6), in human brain
    A T Nies
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Neuroscience 129:349-60. 2004
    ....
  31. ncbi request reprint Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump for steroid sulfates, is an axonal protein of the CNS and peripheral nervous system
    M Bortfeld
    Division of Tumor Biochemistry, German Cancer Research Center, University of Heidelberg, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Neuroscience 137:1247-57. 2006
    ..Our findings may provide a basis for the characterization of mutations in the human ABCC11 gene and their linkage with neurological disorders...
  32. ncbi request reprint Metabolic inactivation of leukotrienes
    D Keppler
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany
    Adv Enzyme Regul 28:307-19. 1989
    ..The interference of leukotriene inactivation in the liver may provide a novel explanation for the ethanol-induced inflammatory reaction in acute alcoholic liver disease...
  33. pmc Multidrug resistance protein-mediated transport of chlorambucil and melphalan conjugated to glutathione
    K Barnouin
    Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Br J Cancer 77:201-9. 1998
    ....
  34. ncbi request reprint Tumor necrosis factor alpha stimulates leukotriene production in vivo
    M Huber
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, FRG
    Eur J Immunol 18:2085-8. 1988
    ..The proinflammatory and shock-inducing LT may mediate many of the adverse effects of TNF in vivo as well as its antitumor action...
  35. ncbi request reprint Expression and localization of the multidrug resistance proteins MRP2 and MRP3 in human gallbladder epithelia
    D Rost
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Gastroenterology 121:1203-8. 2001
    ..Localization of MRP2 and MRP3 may provide an explanation of how the products of phase II conjugation are effluxed from gallbladder epithelia...
  36. pmc Expression of the MRP gene-encoded conjugate export pump in liver and its selective absence from the canalicular membrane in transport-deficient mutant hepatocytes
    R Mayer
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany
    J Cell Biol 131:137-50. 1995
    ..Our results indicate that the absence of Mrp or an isoform of Mrp from the canalicular membrane is the basis for the hereditary defect of the hepatobiliary excretion of anionic conjugates by the transport-deficient hepatocyte...
  37. ncbi request reprint Up-regulation of basolateral multidrug resistance protein 3 (Mrp3) in cholestatic rat liver
    M G Donner
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Hepatology 34:351-9. 2001
    ....
  38. ncbi request reprint Export pumps for glutathione S-conjugates
    D Keppler
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Free Radic Biol Med 27:985-91. 1999
    ..Proteins of the MRP family are indispensable for transport of glutathione S-conjugates and glutathione disulfide into the extracellular space and play, therefore, a decisive role in detoxification and defense against oxidative stress...
  39. ncbi request reprint Analysis of cysteinyl leukotrienes in human urine: enhanced excretion in patients with liver cirrhosis and hepatorenal syndrome
    M Huber
    Deutsches Krebsforschungszentrum, Heidelberg, FRG
    Eur J Clin Invest 19:53-60. 1989
    ..These results indicate that cysteinyl leukotrienes may play an important role in the mediator network responsible for the development of the hepatorenal syndrome in patients with severe liver disease...
  40. ncbi request reprint Characterization and quantification of rat bile phosphatidylcholine by electrospray-tandem mass spectrometry
    W D Lehmann
    Central Spectroscopy, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany
    Anal Biochem 246:102-10. 1997
    ..This suggests an inhibition by cyclosporin A of the translocation of phosphatidylcholine across the hepatocyte canalicular membrane which is mediated by the Mdr2 P-glycoprotein...
  41. doi request reprint Cholestasis and the role of basolateral efflux pumps
    D Keppler
    German Cancer Research Center, Heidelberg, Germany
    Z Gastroenterol 49:1553-7. 2011
    ..This sinusoidal efflux not only enables subsequent renal elimination, but also re-uptake of substances into neighboring and more centrally located hepatocytes in the sinusoid...
  42. pmc Prevention of endogenous leukotriene production during anaphylaxis in the guinea pig by an inhibitor of leukotriene biosynthesis (MK-886) but not by dexamethasone
    A Guhlmann
    Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany
    J Exp Med 170:1905-18. 1989
    ..These studies indicate an important role of cysteinyl LTs in systemic anaphylaxis in vivo and demonstrate the blockade of anaphylactic LT generation by a novel inhibitor of LT biosynthesis (MK-886) but not by dexamethasone...
  43. ncbi request reprint The multidrug resistance protein MRP1 mediates the release of glutathione disulfide from rat astrocytes during oxidative stress
    J Hirrlinger
    Physiologisch chemisches Institut der Universität, Tubingen, Germany
    J Neurochem 76:627-36. 2001
    ..Our data identify rat astrocytes as a MRP1-expressin, brain cell type and demonstrate that this transporter participates in the release of glutathione disulfide from astrocytes during oxidative stress...