Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs
- A. Schinkel, J. Smit, P. Borst
- Biology, ChemistryCell
- 20 May 1994
P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs.
- A. Schinkel, E. Wagenaar, C. Mol, L. van Deemter
- Biology, MedicineJournal of Clinical Investigation
- 1 June 1996
It is shown here that the drugs loperamide, domperidone, and ondansetron are transported substrates for the mouse mdr1a P-GP and its human homologue MDR1, and the possible role that the drug-transporting P- GP(s) may play in the clinical use of many drugs, especially those with potential targets in the central nervous system.
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.
Homozygous disruption of the murine MDR2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease
- J. Smit, A. Schinkel, P. Borst
- Biology, MedicineCell
- 5 November 1993
Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs.
- J. Wijnholds, C. Mol, P. Borst
- Biology, ChemistryProceedings of the National Academy of Sciences…
- 20 June 2000
It is speculated that MRP5 might play a role in some cases of unexplained resistance to thiopurines in acute lymphoblastic leukemia and/or to antiretroviral nucleoside analogs in HIV-infected patients.
Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins.
- A. Schinkel, U. Mayer, P. Borst
- Biology, MedicineProceedings of the National Academy of Sciences…
- 15 April 1997
Mdr1a/1b (-/-) mice should provide a useful model system to further test the pharmacological roles of the drug-transporting P-gps and to analyze the specificity and effectivity of P-gp-blocking drugs.
Increased sensitivity to anticancer drugs and decreased inflammatory response in mice lacking the multidrug resistance-associated protein
- J. Wijnholds, R. Evers, P. Borst
- Biology, ChemistryNature Network Boston
- 1 November 1997
The results suggest that this ubiquitous GS-X pump, which mediates the cellular excretion of many drugs, glutathione S-conjugates of lipophilic xenobiotics and endogenous cysteinyl leukotrienes, is dispensable in mice, making treatment of MDR with MRP-specific reversal agents potentially feasible.
Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier.
- J. Wijnholds, E. C. DeLange, P. Borst
- Biology, MedicineJournal of Clinical Investigation
- 1 February 2000
It is shown that the lack of Mrp1 protein causes etoposide levels to increase about 10-fold in the CSF after intravenous administration of the drug.
Thiopurine metabolism and identification of the thiopurine metabolites transported by MRP4 and MRP5 overexpressed in human embryonic kidney cells.
- P. Wielinga, G. Reid, P. Borst
- Biology, ChemistryMolecular Pharmacology
- 1 December 2002
All major thiopurine monophosphates important in the efficacy of mercaptopurine treatment are transported by MRP4 and MRP5, although the substrate specificity of the two transporters differs in detail.
Specific detection of multidrug resistance proteins MRP1, MRP2, MRP3, MRP5, and MDR3 P-glycoprotein with a panel of monoclonal antibodies.
- G. Scheffer, M. Kool, R. Scheper
- BiologyCancer Research
- 15 September 2000
All Mabs in the panel appeared to be fully specific for their cognate antigens, both in Western blots and cytospin preparations, as revealed by lack of cross-reactivity with any of the other family members.
...
...