The vesicular transport assay: Validated in vitro methods to study drug-mediated inhibition of canalicular efflux transporters ABCB11/BSEP and ABCC2/MRP2

Current Protocols in Toxicology

Volumn 1, Issue SUPPL.54, 2012, Pages

  Herédi Szabó, Krisztina ^a   Kis, Emese ^a   Krajcsi, Peter ^a  

^a SOLVO BIOTECHNOLOGY   (Hungary)

Author keywords

ABCB11 BSEP; ABCC2 MRP2; Canalicular membrane; CDCF; Taurocholate

Indexed keywords

ABC TRANSPORTER; ADENOSINE TRIPHOSPHATE; BILE SALT; CARRIER PROTEIN; MULTIDRUG RESISTANCE PROTEIN 2; XENOBIOTIC AGENT; ABCB11 PROTEIN, HUMAN; BENZBROMARONE; BILE ACID; CYCLOSPORIN; MULTIDRUG RESISTANCE PROTEIN; MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 2;

ARTICLE; CALIBRATION; CONTROLLED STUDY; IN VITRO STUDY; LIQUID CHROMATOGRAPHY; LIVER CELL; MASS SPECTROMETRY; MEMBRANE VESICLE; METABOLITE; PERMEABILITY; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN TRANSPORT; VALIDATION PROCESS; ACTIVE TRANSPORT; CELL MEMBRANE; DRUG ANTAGONISM; DRUG EFFECT; ENZYME SPECIFICITY; HUMAN; METABOLISM; PHYSIOLOGY; REPRODUCIBILITY; TRANSPORT VESICLE;

ATP-BINDING CASSETTE TRANSPORTERS; BENZBROMARONE; BILE ACIDS AND SALTS; BIOLOGICAL TRANSPORT, ACTIVE; CELL MEMBRANE; CYCLOSPORINE; HEPATOCYTES; HUMANS; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; REPRODUCIBILITY OF RESULTS; SUBSTRATE SPECIFICITY; TRANSPORT VESICLES;

EID: 84876023954     PISSN: 19349254     EISSN: 19349262     Source Type: Journal    
DOI: 10.1002/0471140856.tx2304s54     Document Type: Article

References (31)

1. Akita, H., Suzuki, H., Ito, K., Kinoshita, S., Sato, N., Takikawa, H., and Sugiyama, Y. 2001. Characterization of bile acid transport mediated by multidrug resistance associated protein 2 and bile salt export pump. Biochim. Biophys. Acta 1511:7-16.
2. Ansede, J.H., Smith, W.R., Perry, C.H., St Claire, R.L. 3rd, and Brouwer, K.R. 2010. An in vitro assay to assess transporter-based cholestatic hepatotoxicity using sandwich-cultured rat hepatocytes. Drug Metab. Dispos. 38:276-280.
3. Bodo, A., Bakos, E., Szeri, F., Varadi, A., and Sarkadi, B. 2003. Differential modulation of the human liver conjugate transporters MRP2 and MRP3 by bile acids and organic anions. J. Biol. Chem. 278:23529-23537.
4. Byrne, J.A., Strautnieks, S.S., Mieli-Vergani, G., Higgins, C.F., Linton, K.J., and Thompson, R.J. 2002. The human bile salt export pump: Characterization of substrate specificity and identification of inhibitors. Gastroenterology 123:1649-1658.
5. Cosgrove, B.D., King, B.M., Hasan, M.A., Alexopoulos, L.G., Farazi, P.A., Hendriks, B.S.,Griffith, L.G., Sorger, P.K., Tidor, B., Xu, J.J., and Lauffenburger, D.A. 2009. Synergistic drugcytokine induction of hepatocellular death as an in vitro approach for the study of inflammationassociated idiosyncratic drug hepatotoxicity. Toxicol. Appl. Pharmacol. 237:317-330.
6. Dawson, S., Stahl, S., Paul, N., Barber, J., and Kenna, J.G. 2012. In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans. Drug Metab. Dispos. 40:130-138.
7. Gerloff, T., Stieger, B., Hagenbuch, B., Madon, J., Landmann, L., Roth, J., Hofmann, A.F., and Meier, P.J. 1998. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J. Biol. Chem. 273:10046-10050.
8. Glavinas, H., Mehn, D., Jani, M., Oosterhuis, B., Heredi-Szabo, K., and Krajcsi, P. 2008. Utilization of membrane vesicle preparations to study drug-ABC transporter interactions. Exp. Opin. Drug Metab. Toxicol. 4:721-732.
9. Hartman, J.C., Brouwer, K., Mandagere, A., Melvin, L., and Gorczynski, R. 2010. Evaluation of the endothelin receptor antagonists ambrisentan, darusentan, bosentan, and sitaxsentan as substrates and inhibitors of hepatobiliary transporters in sandwich-cultured human hepatocytes. Can. J. Physiol. Pharmacol. 88:682-691.
10. Hayashi, H., Takada, T., Suzuki, H., Onuki, R., Hofmann, A.F., and Sugiyama, Y. 2005. Transport by vesicles of glycine-and taurine-conjugated bile salts and taurolithocholate 3-sulfate:Acomparison of human BSEP with rat Bsep. Biochim. Biophys. Acta 1738:54-62.
11. Heredi-Szabo, K., Kis, E., Molnar, E., Gyorfi, A., and Krajcsi, P. 2008. Characterization of 5(6)-carboxy-2,7-dichlorofluorescein transport by MRP2 and utilization of this substrate as a fluorescent surrogate for LTC4. J. Biomol. Screen. 13:295-301.
12. Heredi-Szabo, K., Glavinas, H., Kis, E., Mehn, D., Bathori, G., Veres, Z., Kobori, L., von Richter, O., Jemnitz, K., and Krajcsi, P. 2009. Multidrug resistance protein 2-mediated estradiol-17beta-D-glucuronide transport potentiation: in vitro-in vivo correlation and species specificity. Drug Metab. Dispos. 37:794-801.
13. Jemnitz, K., Heredi-Szabo, K., Janossy, J., Ioja, E., Vereczkey, L., and Krajcsi, P. 2010a. ABCC2/Abcc2:Amultispecific transporterwith dominant excretory functions. Drug Metab. Rev. 42:402-436.
14. Jemnitz, K., Veres, Z., and Vereczkey, L. 2010b. Contribution of high basolateral bile salt efflux to the lack of hepatotoxicity in rat in response to drugs inducing cholestasis in human. Toxicol. Sci. 115:80-88.
15. Keppler, D., Jedlitschky, G., and Leier, I. 1998. Transport function and substrate specificity of multidrug resistance protein. Methods Enzymol. 292:607-616.
16. Kis, E., Ioja, E., Nagy, T., Szente, L., Heredi-Szabo, K., and Krajcsi, P. 2009a. Effect of membrane cholesterol on BSEP/Bsep activity: Species specificity studies for substrates and inhibitors. Drug Metab. Dispos. 37:1878-1886.
17. Kis, E., Rajnai, Z., Ioja, E., Heredi Szabo, K., Nagy, T.,Mehn, D., and Krajcsi, P. 2009b. Mouse Bsep ATPase assay: A nonradioactive tool for assessment of the cholestatic potential of drugs. J. Biomol. Screen. 14:10-15.
18. Kis, E., Ioja, E., Rajnai, Z., Jani, M., Mehn, D., Heredi-Szabo, K., and Krajcsi, P. 2011. BSEP inhibition -In vitro screens to assess cholestatic potential of drugs. Toxicol. In Vitro. In press.
19. Kostrubsky, S.E., Strom, S.C., Kalgutkar, A.S., Kulkarni, S., Atherton, J., Mireles, R., Feng, B., Kubik, R., Hanson, J.,Urda, E., and Mutlib, A.E. 2006. Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone. Toxicol. Sci. 90:451-459.
20. Krahenbuhl, S., Talos, C., Fischer, S., and Reichen, J. 1994. Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria. Hepatology 19:471-479.
21. Letschert, K., Komatsu, M., Hummel-Eisenbeiss, J., and Keppler, D. 2005. 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. J. Pharmacol. Exp. Ther. 313:549-556.
22. Maillette de Buy Wenniger, L. and Beuers, U. 2010. Bile salts and cholestasis. Dig. Liver Dis. 42:409-418.
23. Matsushima, S., Maeda, K., Kondo, C., Hirano, M., Sasaki, M., Suzuki, H., and Sugiyama, Y. 2005. Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistanceassociated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein. J. Pharmacol. Exp. Ther. 314:1059-1067.
24. Mita, S., Suzuki, H., Akita, H., Stieger, B., Meier, P.J., Hofmann, A.F., and Sugiyama, Y. 2005. Vectorial transport of bile salts across MDCK cells expressing both rat Na+-taurocholate cotransporting polypeptide and rat bile salt export pump. Am. J. Physiol. Gastrointest. Liver Physiol. 288:G159-G167.
25. Mita, S., Suzuki, H., Akita, H., Hayashi, H., Onuki, R.,Hofmann, A.F., and Sugiyama, Y. 2006.Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat Ntcp and Bsep. Am. J. Physiol. Gastrointest. Liver Physiol. 290:G550-G556.
26. Morgan, R.E., Trauner, M., van Staden, C.J., Lee, P.H., Ramachandran, B., Eschenberg, M., Afshari, C.A., Qualls, C.W. Jr., Lightfoot-Dunn, R., and Hamadeh, H.K. 2010. Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol. Sci. 118:485-500.
27. Noe, J., Stieger, B., and Meier, P.J. 2002. Functional expression of the canalicular bile salt export pump of human liver. Gastroenterology 123:1659-1666. Pessayre, D., Berson, A., Fromenty, B., and Mansouri, A. 2001. Mitochondria in steatohepatitis. Semin. Liver Dis. 21:57-69.
28. Pessayre, D., Berson, A., Fromenty, B., and Mansouri, A. 2001. Mitochondria in steatohepatitis. Semin. Liver Dis. 21:57-69.
29. Rius, M., Hummel-Eisenbeiss, J., and Keppler, D. 2008. ATP-dependent transport of leukotrienes B4 and C4 by the multidrug resistance protein ABCC4 (MRP4). J. Pharmacol. Exp. Ther. 324:86-94.
30. Swift, B., Pfeifer, N.D., and Brouwer, K.L. 2010. Sandwich-cultured hepatocytes: An in vitro model to evaluate hepatobiliary transporter-based drug interactions and hepatotoxicity. Drug Metab. Rev. 42:446-471.
31. Zelcer, N., Huisman, M.T., Reid, G., Wielinga, P., Breedveld, P., Kuil, A., Knipscheer, P., Schellens, J.H., Schinkel, A.H., and Borst, P. 2003. Evidence for two interacting ligand binding sites in human multidrug resistance protein 2 (ATP binding cassette C2). J. Biol. Chem. 278:23538-