A. H. Schinkel

Running title: Mrp2 (Abcc2) knockout mice Corresponding author: (2008)

K. Mohrmann, E. Wagenaar, J. S. Lagas, ...

Number of text pages: 35 (excluding title pages) Number of tables: 0 Number of figures: 7 Number of references: 40 Number of words in Abstract: 250

Carcinogen and anticancer drug transport by Mrp2 in vivo: studies using Mrp2 (Abcc2) knockout mice (2006)

Vlaming, M.L.H., Mohrmann, K., Wagenaar, E., Waart, D.R. De, Lagas, J.S., ...

The Breast Cancer Resistance Protein (BCRP/ABCG2) concentrates drugs and carcinogenic xenotoxins into milk. (2005)

Dale, Trevor Clive, Jonker, J.W., Mesman, E., Schinkel, A.H.

The Breast Cancer Resistance Protein (BCRP/ABCG2) concentrates drugs and carcinogenic xenotoxins into milk. (2005)

Dale, Trevor Clive, Jonker, J.W., Mesman, E., Schinkel, A.H.

MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid (2005)

Huisman, M.T., Chhatta, A.A., Tellingen, O. Van, Beijnen, J.H., Schinkel, A.H.

P glycoprotein in human immunodeficiency virus type 1 infection and therapy (2004)

Sankatsing, S.U., Beijnen, J.H., Schinkel, A.H., Lange, J.M.A., Prins, J.M.

The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria (2002)

Jonker, J.W., Buitelaar, M., Wagenaar, E., Valk, M. Van Der, Scheffer, G.L., Scheper, R.J., ...

Inhibition of BCRP-mediated Drug Efflux by Fumitremorgin-type Indolyl Diketopiperazines. (2001)

Loevezijn, A. Van, Allen, J.D., Schinkel, A.H., Koomen, G.J.

New Nucleoside analogues, Synthesis and Biological Properties. (2000)

Loevezijn, A. Van, Allen, J.D., Schinkel, A.H., Koomen, G.J.

Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier (2000)

Wijnholds, J., Scheffer, G.L., Valk, M. Van Der, ...

Extensive contribution of the multidrug transporters P-glycoprotein and Mrp1 to basal drug resistance (2000)

Allen, J.D., Brinkhuis, R.F., Deemter, L. Van, Wijnholds, J., Schinkel, A.H.

New physiological functions for drug-transporting P-glycoproteins? (1998)

Borst, P., Blitterswijk, W.J. Van, Borst, J., Tepper, A.D., Schinkel, A.H.

Full blockade of intestinal P-glycoprotein and extensive inhibition of blood-brain barrier P-glycoprotein by oral treatment of mice with PSC833 (1998)

Mayer, U., Wagenaar, E., Dorobek, B., Beijnen, J.H., Borst, P., Schinkel, A.H.

P-glycoprotein, a guardian of the brain (1998)

Borst, P., Schinkel, A.H.

Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA (1998)

Evers, R., Kool, M., Deemter, L. Van, Janssen, H., Calafat, J., ...

Hepatocyte-specific expression of the human MDR3 P-glycoprotein gene restores the biliary phosphatidylcholine excretion absent in Mdr2 (-/-) mice (1998)

Smith, A.J., Ottenhoff, R., Schinkel, A.H., Borst, P.

Availability of PSC833, a substrate and inhibitor of poglycoproteins, in various concentrations of serum (1998)

Smith, A.J., Mayer, U., Schinkel, A.H., Borst, P.

New physiological functions for drugtransporting P-glycoproteins (1998)

Borst, P., Blitterswijk, W.J. Van, Borst, J., Tepper, A.D., Schinkel, A.H.

Hepatocyte-specific expression of the human MDR3 P-glycoprotein gene restores in the bilary phosphatidylcholine excretion absent in Mdr2 (-/-) mice (1998)

Smith, A.J., Vree, M. De, Ottenhoff, R., Schinkel, A.H., Borst, P.

Borderline pathology in mdr2 (-/-) rescue mice: a new model to study non-suppurative cholangitis (1997)

Vree, M. De, Smith, A.J., Ottenhoff, R., Schinkel, A.H., Borst, P., ...

Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine (1997)

Sparreboom, A., Asperen, J. Van, Mayer, U., Schinkel, A.H., Smit, J.W., Meijer, D.K.F., ...

Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins (1997)

Schinkel, A.H., Mayer, U., Wagenaar, E., Deemter, L. Van, Smit, J.J.M., ...

The physiological role of mdr2 P-glycoprotein in hepatobiliary phospholipid transport (1997)

Smit, J.J.M., Schinkel, A.H., Ottenhoff, R., Offerhaus, G.J.A., ...

Genetic dissection of the function of mammalian P-glycoproteins (1997)

Borst, P., Schinkel, A.H.

Enhanced oral bioavailability of paclitaxel in mice treated with P-glycoprotein blocker SDZ 833 (1997)

Asperen, J. Van, Tellingen, O. Van, Sparreboom, A., Schinkel, A.H., Borst, P., Nooijen, W.J., ...

Rna-Polymerase Induces DNA Bending at Yeast Mitochondrial Promoters (1988)

Schinkel, A.H., Tabak, H.F.

Effect of point mutations on in vitro transcription from the promoter for the large ribosomal RNA gene of yeast mitochondria (1987)

Schinkel, A.H., Stuiver, M.H., Tabak, H.F.

Initiation of transcription on mitochondrial DNA of Saccharomyces cerevisiae was studied in an in vitro system with a mtRNA polymerase fraction reconstituted from separately purified components and...

The human multidrug resistance-associated protein functionally complements the yeast cadmium resistance factor 1.

Tommasini, R, Evers, R, Vogt, E, Mornet, C, Zaman, G J, Schinkel, A H, ...

A Saccharomyces cerevisiae strain with a disrupted yeast cadmium resistance factor (YCF1) gene (DTY168) is hypersensitive to cadmium. YCF1 resembles the human multidrug resistance-associated protein...

P-glycoprotein: a major determinant of rifampicin-inducible expression of cytochrome P4503A in mice and humans.

Schuetz, E G, Schinkel, A H, Relling, M V, Schuetz, J D

The P-glycoprotein (Pgp) efflux pump can influence the hepatocellular concentration of xenobiotics that are modulators and substrates of cytochrome P4503A (CYP3A). We tested the hypothesis that Pgp...

Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A.

Schinkel, A H, Wagenaar, E, Van Deemter, L, Mol, C A, Borst, P

We have previously shown that absence of the mouse mdr1a (also called mdr3) P-glycoprotein in mdr1a (-/-) "knockout" mice has a profound effect on the tissue distribution and elimination of...

Regulation of biliary lipid secretion by mdr2 P-glycoprotein in the mouse.

Oude Elferink, R P, Ottenhoff, R, Van Wijland, M, Smit, J J, Schinkel, A H, Groen, A K

Disruption of the mdr2 gene in mice leads to a complete absence of phospholipid from bile (Smit, J. J. M., et al. 1993. Cell. 75:451-462). We have investigated the control of both mdr2 P-glycoprotein...

Effect of point mutations on in vitro transcription from the promoter for the large ribosomal RNA gene of yeast mitochondria.

Schinkel, A H, Groot Koerkamp, M J, Stuiver, M H, Van Der Horst, G T, Tabak, H F

Initiation of transcription on mitochondrial DNA of Saccharomyces cerevisiae was studied in an in vitro system with a mtRNA polymerase fraction reconstituted from separately purified components and...

RNA polymerase induces DNA bending at yeast mitochondrial promoters.

Schinkel, A H, Groot Koerkamp, M J, Teunissen, A W, Tabak, H F

Yeast mitochondrial RNA polymerase can bind specifically to promoter-containing DNA fragments in vitro as detected by DNAse I or methidiumpropyl-EDTA. Fe(II) protection assays and gel retardation...

Mitochondrial RNA polymerase of Saccharomyces cerevisiae: composition and mechanism of promoter recognition.

Schinkel, A H, Groot Koerkamp, M J, Tabak, H F

Mitochondrial RNA polymerase of Saccharomyces cerevisiae consists of two different proteins: a core RNA polymerase of 145 kd and a specificity factor of 43 kd, which contributes the capacity to...

Basolateral localization and export activity of the human multidrug resistance-associated protein in polarized pig kidney cells.

Evers, R, Zaman, G J, Van Deemter, L, Jansen, H, Calafat, J, Oomen, L C, ...

The human multidrug resistance-associated protein MRP confers resistance to various cytotoxic drugs by lowering the intracellular drug concentration. Recent evidence indicates that MRP can also...

P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs.

Schinkel, A H, Wagenaar, E, Mol, C A, Van Deemter, L

The mouse mdr1a (also called mdr3) P-GP is abundant in the blood-brain barrier, and its absence in mdr1a (-/-) mice leads to highly increased levels of the drugs ivermectin, vinblastine, digoxin, and...

Full blockade of intestinal P-glycoprotein and extensive inhibition of blood-brain barrier P-glycoprotein by oral treatment of mice with PSC833.

Mayer, U, Wagenaar, E, Dorobek, B, Beijnen, J H, Borst, P, Schinkel, A H

Mice lacking mdr1-type P-glycoproteins (mdr1a/1b [-/-] mice) display large changes in the pharmacokinetics of digoxin and other drugs. Using the kinetics of digoxin in mdr1a/1b (-/-) mice as a model...

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

Evers, R, Kool, M, Van Deemter, L, Janssen, H, Calafat, J, Oomen, L C, ...

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...

Characterization of the promoter of the large ribosomal RNA gene in yeast mitochondria and separation of mitochondrial RNA polymerase into two different functional components.

Schinkel, A H, Groot Koerkamp, M J, Van Der Horst, G T, Touw, E P, Osinga, K A, Van Der Bliek, A M, ...

We have characterized a DNA sequence that functions in recognition of the promoter of the mitochondrial large rRNA gene by the yeast mtRNA polymerase. Promoter-containing DNA fragments were...

The human multidrug resistance-associated protein functionally complements the yeast cadmium resistance factor 1.

Tommasini, R, Evers, R, Vogt, E, Mornet, C, Zaman, G J, Schinkel, A H, ...

A Saccharomyces cerevisiae strain with a disrupted yeast cadmium resistance factor (YCF1) gene (DTY168) is hypersensitive to cadmium. YCF1 resembles the human multidrug resistance-associated protein...

P-glycoprotein: a major determinant of rifampicin-inducible expression of cytochrome P4503A in mice and humans.

Schuetz, E G, Schinkel, A H, Relling, M V, Schuetz, J D

The P-glycoprotein (Pgp) efflux pump can influence the hepatocellular concentration of xenobiotics that are modulators and substrates of cytochrome P4503A (CYP3A). We tested the hypothesis that Pgp...

Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A.

Schinkel, A H, Wagenaar, E, Van Deemter, L, Mol, C A, Borst, P

We have previously shown that absence of the mouse mdr1a (also called mdr3) P-glycoprotein in mdr1a (-/-) "knockout" mice has a profound effect on the tissue distribution and elimination of...

Regulation of biliary lipid secretion by mdr2 P-glycoprotein in the mouse.

Oude Elferink, R P, Ottenhoff, R, Van Wijland, M, Smit, J J, Schinkel, A H, Groen, A K

Disruption of the mdr2 gene in mice leads to a complete absence of phospholipid from bile (Smit, J. J. M., et al. 1993. Cell. 75:451-462). We have investigated the control of both mdr2 P-glycoprotein...

Effect of point mutations on in vitro transcription from the promoter for the large ribosomal RNA gene of yeast mitochondria.

Schinkel, A H, Groot Koerkamp, M J, Stuiver, M H, Van Der Horst, G T, Tabak, H F

Initiation of transcription on mitochondrial DNA of Saccharomyces cerevisiae was studied in an in vitro system with a mtRNA polymerase fraction reconstituted from separately purified components and...

RNA polymerase induces DNA bending at yeast mitochondrial promoters.

Schinkel, A H, Groot Koerkamp, M J, Teunissen, A W, Tabak, H F

Yeast mitochondrial RNA polymerase can bind specifically to promoter-containing DNA fragments in vitro as detected by DNAse I or methidiumpropyl-EDTA. Fe(II) protection assays and gel retardation...

Mitochondrial RNA polymerase of Saccharomyces cerevisiae: composition and mechanism of promoter recognition.

Schinkel, A H, Groot Koerkamp, M J, Tabak, H F

Mitochondrial RNA polymerase of Saccharomyces cerevisiae consists of two different proteins: a core RNA polymerase of 145 kd and a specificity factor of 43 kd, which contributes the capacity to...

Basolateral localization and export activity of the human multidrug resistance-associated protein in polarized pig kidney cells.

Evers, R, Zaman, G J, Van Deemter, L, Jansen, H, Calafat, J, Oomen, L C, ...

The human multidrug resistance-associated protein MRP confers resistance to various cytotoxic drugs by lowering the intracellular drug concentration. Recent evidence indicates that MRP can also...

P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs.

Schinkel, A H, Wagenaar, E, Mol, C A, Van Deemter, L

The mouse mdr1a (also called mdr3) P-GP is abundant in the blood-brain barrier, and its absence in mdr1a (-/-) mice leads to highly increased levels of the drugs ivermectin, vinblastine, digoxin, and...

Full blockade of intestinal P-glycoprotein and extensive inhibition of blood-brain barrier P-glycoprotein by oral treatment of mice with PSC833.

Mayer, U, Wagenaar, E, Dorobek, B, Beijnen, J H, Borst, P, Schinkel, A H

Mice lacking mdr1-type P-glycoproteins (mdr1a/1b [-/-] mice) display large changes in the pharmacokinetics of digoxin and other drugs. Using the kinetics of digoxin in mdr1a/1b (-/-) mice as a model...

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

Evers, R, Kool, M, Van Deemter, L, Janssen, H, Calafat, J, Oomen, L C, ...

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...

Characterization of the promoter of the large ribosomal RNA gene in yeast mitochondria and separation of mitochondrial RNA polymerase into two different functional components.

Schinkel, A H, Groot Koerkamp, M J, Van Der Horst, G T, Touw, E P, Osinga, K A, Van Der Bliek, A M, ...

We have characterized a DNA sequence that functions in recognition of the promoter of the mitochondrial large rRNA gene by the yeast mtRNA polymerase. Promoter-containing DNA fragments were...

Complete in vivo reversal of P-glycoprotein pump function in the blood-brain barrier visualized with positron emission tomography

Hendrikse, N H, Schinkel, A H, Fluks, E, Willemsen, A T M, ...

Homozygously mdr1a gene disrupted mice (mdr1a(−/−) mice) and wild type mice (mdr1a(+/+) mice) were used to develop a method for P-glycoprotein (P-gp) function imaging non-invasively and to study...

Role of blood-brain barrier P-glycoprotein in limiting brain accumulation and sedative side-effects of asimadoline, a peripherally acting analgaesic drug

Jonker, J W, Wagenaar, E, Van Deemter, L, Gottschlich, R, Bender, H M, Dasenbrock, J, ...

Studies with knockout mice lacking mdr1a P-glycoprotein (P-gp) have previously shown that blood-brain barrier P-gp is important in preventing the accumulation of several drugs in the...

Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr 1a P-glycoprotein.

Mayer, U., Wagenaar, E., Beijnen, J. H., Smit, J. W., Meijer, D. K., Van Asperen, J., ...

1. We have used mice with a disrupted mdr 1a P-glycoprotein gene (mdr 1a (-/-) mice) to study the role of P-glycoprotein in the pharmacokinetics of digoxin, a model P-glycoprotein substrate. 2....

Enhanced oral bioavailability of paclitaxel in mice treated with the P-glycoprotein blocker SDZ PSC 833.

Van Asperen, J., Van Tellingen, O., Sparreboom, A., Schinkel, A. H., Borst, P., Nooijen, W. J., ...

Inhibition of intestinal P-glycoprotein might enhance the absorption of orally administered P-glycoprotein substrate drugs. We show here a 10-fold increased oral bioavailability of paclitaxel in mice...

Increased accumulation of doxorubicin and doxorubicinol in cardiac tissue of mice lacking mdr1a P-glycoprotein

Asperen, J Van, Tellingen, O Van, Tijssen, F, Schinkel, A H, Beijnen, J H

To gain more insight into the pharmacological role of endogenous P-glycoprotein in the metabolism of the widely used substrate drug doxorubicin, we have studied the plasma pharmacokinetics, tissue...