Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA

The Journal of Clinical Investigation
R EversP Borst

Abstract

The canalicular (apical) membrane of the hepatocyte contains an ATP-dependent transport system for organic anions, known as the multispecific organic anion transporter (cMOAT). The deduced amino acid sequence of cMOAT is 49% identical to that of the human multidrug resistance- associated protein (MRP) MRP1, and cMOAT and MRP1 are members of the same sub-family of adenine nucleotide binding cassette transporters. In contrast to MRP1, cMOAT was predominantly found intracellularly in nonpolarized cells, suggesting that cMOAT requires a polarized cell for plasma membrane routing. Therefore, we expressed cMOAT cDNA in polarized kidney epithelial MDCK cell lines. When these cells are grown in a monolayer, cMOAT localizes to the apical plasma membrane. We demonstrate that cMOAT causes transport of the organic anions S-(2,4-dinitrophenyl)-glutathione, the glutathione conjugate of ethacrynic acid, and S-(PGA1)-glutathione, a substrate not shown to be transported by organic anion transporters previously. Transport is inhibited only inefficiently by compounds known to block MRP1. We also show that cMOAT causes transport of the anticancer drug vinblastine to the apical side of a cell monolayer. We conclude that cMOAT is a 5'-adenosine trip...Continue Reading

References

Oct 25, 1978·Biochimica Et Biophysica Acta·A ChaudhariT E Eling
Jan 1, 1992·Annual Review of Cell Biology·C F Higgins
Nov 1, 1992·Trends in Biochemical Sciences·T Ishikawa
Jul 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·D Louvard
Jul 17, 1995·Biochimica Et Biophysica Acta·R P Oude ElferinkG M Groothuis
Aug 15, 1995·Proceedings of the National Academy of Sciences of the United States of America·G J ZamanP Borst
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·G J ZamanH J Broxterman
Jan 1, 1993·Annual Review of Biochemistry·M M Gottesman, I Pastan
Jan 1, 1995·Annual Review of Microbiology·P Borst, M Ouellette
May 1, 1996·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J KartenbeckD Keppler
Jun 1, 1996·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·D W LoeS P Cole
Jan 1, 1995·Annual Review of Genetics·M M GottesmanI Pastan
Aug 1, 1996·Human Gene Therapy·T M Kinsella, G P Nolan
Jun 1, 1997·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C C PaulusmaR P Oude Elferink

❮ Previous
Next ❯

Citations

Mar 12, 2011·The Journal of Antimicrobial Chemotherapy·Nadine Cécile Luise ZembruskiJohanna Weiss
Jan 16, 2008·Antimicrobial Agents and Chemotherapy·Jurjen S LagasAlfred H Schinkel
Dec 30, 2010·Antimicrobial Agents and Chemotherapy·Nadine Cécile Luise ZembruskiJohanna Weiss
Nov 22, 2011·Chinese Journal of Cancer·Kamlesh SodaniZhe-Sheng Chen
Nov 2, 2001·Biochemical and Biophysical Research Communications·C FernettiC Tiribelli
Jul 11, 2002·The Lancet Oncology·Joost BartElisabeth G E de Vries
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·M KoolP Borst
Dec 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·K YuD M Ornitz
Jul 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Glen ReidPiet Borst
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·M E PerkinsS M Le Blancq
Jun 7, 2000·Proceedings of the National Academy of Sciences of the United States of America·J WijnholdsP Borst
Sep 16, 2000·European Journal of Pharmacology·R A Van AubelF G Russel
Jan 22, 2003·Advanced Drug Delivery Reviews·Yan ZhangDonald W Miller
Aug 22, 2000·European Journal of Biochemistry·H V WesterhoffA P Jongsma
Jun 28, 2002·Lancet·Christoph G DietrichCarsten Gartung
May 26, 2009·European Journal of Drug Metabolism and Pharmacokinetics·Hani Al-SalamiMomir Mikov
Sep 1, 2006·European Journal of Clinical Pharmacology·Hua-Wen XinUlrich Klotz
Sep 2, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Oliver von RichterKarl Zech
Oct 19, 2007·Investigational New Drugs·Murugesan K GounderEric H Rubin
Apr 23, 2005·Pharmaceutical Research·Masakazu HirouchiYuichi Sugiyama
Apr 2, 2013·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Cristina BolzatiNicola Antonio Colabufo
Jan 7, 2004·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Jan TaipalensuuPer Artursson
Jan 7, 2004·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Lauretta M S ChanBarry H Hirst
Mar 23, 2005·The Journal of Cell Biology·Alka MansukhaniClaudio Basilico

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.