The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Pregnane X Receptor Up-Regulation of P-Glycoprotein Expression and Transport Function at the Blood-Brain Barrier
Abstract
P-glycoprotein, an ATP-driven drug export pump, is a critical, selective component of the blood-brain barrier responsible for the poor penetration of many therapeutic drugs. In liver, ligand-activated, nuclear receptors are transcriptional regulators of drug metabolizing enzymes and drug export pumps, but only one, the pregnane X receptor (PXR in rodents, SXR in humans), regulates p-glycoprotein expression. We report for the first time that PXR is expressed in rat brain capillaries. Moreover, exposing isolated capillaries to the PXR ligands pregnenolone-16alpha-carbonitrile (PCN) and dexamethasone increased p-glycoprotein expression and p-glycoprotein-specific transport of a fluorescent cyclosporine A derivative into capillary lumens. Dosing rats with PCN and dexamethasone increased p-glycoprotein expression in liver plasma membranes and in brain capillaries and up-regulated specific transport in capillaries. This is the first evidence for PXR expression in brain and for regulation by nuclear receptors of a xenobiotic export pump at the blood-brain barrier. These results imply selective tightening of the barrier in patients exposed to the wide range of xenobiotics that are PXR/SXR ligands, including drugs, dietary constituents, and toxicants.
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Cites
Kast, H. R., Goodwin, B., Tarr, P. T., Jones, S. A., Anisfeld, A. M., Stoltz, C. M., Tontonoz, P., Kliewer, S., Willson, T. M., & Edwards, P. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109326200 · Cited by 916
Cited by
Astrocyte-endothelial interactions at the blood-brain barrier
Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595
Shawahna, R., Uchida, Y., Declèves, X., Ohtsuki, S., Yousif, S., Dauchy, S., Jacob, A., Chassoux, F., Daumas-Duport, C., Couraud, P.-O., et al. (2011) · Molecular Pharmaceutics · doi:10.1021/mp200129p · Cited by 372
Modulation of P-glycoprotein efflux pump: induction and activation as a therapeutic strategy
Silva, R., Vilas-Boas, V., Carmo, H., Dinis-Oliveira, R. J., Carvalho, F., de Lourdes Bastos, M., & Remião, F. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.11.013 · Cited by 339
Nuclear receptors CAR and PXR: Molecular, functional, and biomedical aspects
di Masi, A., Marinis, E. D., Ascenzi, P., & Marino, M. (2009) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2009.04.002 · Cited by 288
Bauer, B., Hartz, A. M. S., & Miller, D. S. (2007) · Molecular Pharmacology · doi:10.1124/mol.106.029512 · Cited by 275
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Metadata
- Authors
- Bauer, B., Hartz, A. M. S., Fricker, G., & Miller, D. S.
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 2004-09
- Volume
- 66
- Issue
- 3
- Pages
- 413-419
- ISSN
- 0026-895X (ISSN-L)
- OpenAlex
- W2153507776
- Cited by
- 294
- References
- 1
- FWCI
- 6.61
- Type
- journal article
- Language
- en
- Open access
- closed
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- Bauer, B., Hartz, A. M. S., Fricker, G., & Miller, D. S. (2004). Pregnane X Receptor Up-Regulation of P-Glycoprotein Expression and Transport Function at the Blood-Brain Barrier. Molecular Pharmacology. https://doi.org/10.1016/s0026-895x(24)05623-2
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