The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier
Open accessAbstract
Multidrug resistance protein 1 (MRP1) is a transporter protein that helps to protect normal cells and tumor cells against the influx of certain xenobiotics. We previously showed that Mrp1 protects against cytotoxic drugs at the testis-blood barrier, the oral epithelium, and the kidney urinary collecting duct tubules. Here, we generated Mrp1/Mdr1a/Mdr1b triple-knockout (TKO) mice, and used them together with Mdr1a/Mdr1b double-knockout (DKO) mice to study the contribution of Mrp1 to the tissue distribution and pharmacokinetics of etoposide. We observed increased toxicity in the TKO mice, which accumulated etoposide in brown adipose tissue, colon, salivary gland, heart, and the female urogenital system. Immunohistochemical staining revealed the presence of Mrp1 in the oviduct, uterus, salivary gland, and choroid plexus (CP) epithelium. To explore the transport function of Mrp1 in the CP epithelium, we used TKO and DKO mice cannulated for cerebrospinal fluid (CSF). We show here that the lack of Mrp1 protein causes etoposide levels to increase about 10-fold in the CSF after intravenous administration of the drug. Our results indicate that Mrp1 helps to limit tissue distribution of certain drugs and contributes to the blood-CSF drug-permeability barrier.
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Citations
Cites
Overexpression of a Transporter Gene in a Multidrug-Resistant Human Lung Cancer Cell Line
Cole, S. P. C., Bhardwaj, G., Gerlach, J. H., Mackie, J. E., Grant, C. E., Almquist, K. C., Stewart, A. J., Kurz, E. U., Duncan, A. M. V., & Deeley, R. G. (1992) · Science · doi:10.1126/science.1360704 · Cited by 3,037
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A family of drug transporters: the multidrug resistance-associated proteins
Borst, P., Evers, R., Kool, M., & Wijnholds, J. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.16.1295 · Cited by 1,751
Self-citationOvercoming the blood–brain tumor barrier for effective glioblastoma treatment
van Tellingen, O., Yetkin-Arik, B., de Gooijer, M. C., Wesseling, P., Wurdinger, T., & de Vries, H. E. (2015) · Drug Resistance Updates · doi:10.1016/j.drup.2015.02.002 · Cited by 1,035
Blood-brain barrier active efflux transporters: ATP-binding cassette gene family
Löscher, W., & Potschka, H. (2005) · NeuroRX · doi:10.1602/neurorx.2.1.86 · Cited by 872
Deeley, R. G., Westlake, C., & Cole, S. P. C. (2006) · Physiological Reviews · doi:10.1152/physrev.00035.2005 · Cited by 761
The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses
Deeken, J. F., & Löscher, W. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2854 · Cited by 721
Metadata
- Authors
- Wijnholds, J., de Lange, E. C. M., Scheffer, G. L., van den Berg, D.-J., Mol, C. A. A. M., van der Valk, M., Schinkel, A. H., Scheper, R. J., Breimer, D. D., & Borst, P.
- Venue
- Journal of Clinical Investigation
- Published
- 2000-02-01
- Volume
- 105
- Issue
- 3
- Pages
- 279-285
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2153338237
- Cited by
- 360
- References
- 1
- FWCI
- 12.83
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Wijnholds, J., de Lange, E. C. M., Scheffer, G. L., van den Berg, D.-J., Mol, C. A. A. M., van der Valk, M., Schinkel, A. H., Scheper, R. J., Breimer, D. D., & Borst, P. (2000). Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier. Journal of Clinical Investigation. https://doi.org/10.1172/jci8267
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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