Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs
Mammalian ABC transporters in health and disease.
This work focuses on three topics: ABC transporters transporting drugs (xenotoxins) and drug conjugates, and a rapidly increasing number of ABC Transporters found to play a role in lipid transport.
A family of drug transporters: the multidrug resistance-associated proteins.
- P. Borst, R. Evers, M. Kool, J. Wijnholds
- BiologyJournal of the National Cancer Institute
- 16 August 2000
Whether long-term inhibition of MRPs in humans can be tolerated (assuming that suitable inhibitors will be found) remains to be determined.
Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A.
- A. Schinkel, E. Wagenaar, L. van Deemter, C. Mol, P. Borst
- Biology, MedicineJournal of Clinical Investigation
- 1 October 1995
It is shown that the mouse mdr1a and the human MDR1 P-glycoprotein actively transport ivermectin, dexamethasone, digoxin, and cyclosporin A and, to a lesser extent, morphine across a polarized kidney epithelial cell layer in vitro.
Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines.
It is found that even in cells selected for a low level of resistance, several MRP-related genes can be up-regulated simultaneously, and the need for gene-specific blocks in gene expression to define which transporter contributes to resistance in each resistant cell line is emphasized.
The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs
Investigation of the interaction between prostaglandins and members of the ATP-binding cassette (ABC) transporter ABCC [multidrug resistance protein (MRP)] family of membrane export pumps suggests that MRP4 can release prostaglandsins from cells, and that some nonsteroidal antiinflammatory drugs might also act by inhibiting this release.
Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA.
It is shown that cMOAT causes transport of the organic anions S-(2,4-dinitrophenyl)-glutathione, the glutathione conjugate of ethacrynic acid, and S-(PGA1)-gluten, a substrate not shown to be transported by organic anion transporters previously.
Congenital Jaundice in Rats with a Mutation in a Multidrug Resistance-Associated Protein Gene
The complementary DNA for rat cmoat, a homolog of the human multidrug resistance gene (hMRP1), was isolated and shown to be expressed in the canalicular membrane of hepatocytes and likely accounts for the TR− phenotype.
MRP3, an organic anion transporter able to transport anti-cancer drugs.
- M. Kool, M. P. van der Linden, P. Borst
- BiologyProceedings of the National Academy of Sciences…
- 8 June 1999
MRP3 is an organic anion and multidrug transporter, like the GS-X pumps MRP1 and MRP2, and in Madin-Darby canine kidney II cells, MRP3 routes to the basolateral membrane and mediates transport of the organicAnion S-(2,4-dinitrophenyl-)glutathione toward the basoliateral side of the monolayer.