| | |  | | | | Record from Web of Science® | | | | | | |
| Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA |
|
|
| Author(s): Evers R, Kool M, van Deemter L, Janssen H, Calafat J, Oomen LCJM, Paulusma CC, Elferink RPJO, Baas F, Schinkel AH, Borsi P |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 101 Issue: 7 Pages: 1310-1319 Published: APR 1 1998 |
| Times Cited: 300 References: 59 |
| Abstract: The canalicular (apical) membrane of the hepatocyte contains arm 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 io 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-(PGA(1))-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 triphosphate binding cassette transporter that potentially might be involved in drug resistance in mammalian cells. |
| Document Type: Article |
| Language: English |
| Reprint Address: Borsi, P (reprint author), Netherlands Canc Inst, Antoni Van Leeuwenhoek Huis, Div Mol Biol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands |
Addresses:
1. Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands
2. Netherlands Canc Inst, Div Cell Biol, NL-1066 CX Amsterdam, Netherlands
3. Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol, NL-1105 AZ Amsterdam, Netherlands
4. Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: ZF791 |
| ISSN: 0021-9738 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |