Modulation of p-glycoprotein transport function at the blood-brain barrier
- PMID: 15673560
- DOI: 10.1177/153537020523000206
Modulation of p-glycoprotein transport function at the blood-brain barrier
Abstract
The central nervous system (CNS) effects of many therapeutic drugs are blunted because of restricted entry into the brain. The basis for this poor permeability is the brain capillary endothelium, which comprises the blood-brain barrier. This tissue exhibits very low paracellular (tight-junctional) permeability and expresses potent, multispecific, drug export pumps. Together, these combine to limit use of pharmacotherapy to treat CNS disorders such as brain cancer and bacterial or viral infections. Of all the xenobiotic efflux pumps highly expressed in brain capillary endothelial cells, p-glycoprotein handles the largest fraction of commonly prescribed drugs and thus is an obvious target for manipulation. Here we review recent studies focused on understanding the mechanisms by which p-glycoprotein activity in the blood-brain barrier can be modulated. These include (i) direct inhibition by specific competitors, (ii) functional modulation, and (iii) transcriptional modulation. Each has the potential to specifically reduce p-glycoprotein function and thus selectively increase brain permeability of p-glycoprotein substrates.
Similar articles
-
Modulation of P-glycoprotein at the blood-brain barrier: opportunities to improve central nervous system pharmacotherapy.Pharmacol Rev. 2008 Jun;60(2):196-209. doi: 10.1124/pr.107.07109. Epub 2008 Jun 17. Pharmacol Rev. 2008. PMID: 18560012 Free PMC article. Review.
-
Constitutive androstane receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier.Mol Pharmacol. 2010 Sep;78(3):376-83. doi: 10.1124/mol.110.063685. Epub 2010 Jun 14. Mol Pharmacol. 2010. PMID: 20547735 Free PMC article.
-
Drug transport to the brain: key roles for the efflux pump P-glycoprotein in the blood-brain barrier.Vascul Pharmacol. 2002 Jun;38(6):339-48. doi: 10.1016/s1537-1891(02)00201-x. Vascul Pharmacol. 2002. PMID: 12529928 Review.
-
P-glycoprotein-mediated efflux transport of anticancer drugs at the blood-brain barrier.Ther Drug Monit. 1998 Oct;20(5):588-90. doi: 10.1097/00007691-199810000-00024. Ther Drug Monit. 1998. PMID: 9780140 Review.
-
PET Studies on P-glycoprotein function in the blood-brain barrier: how it affects uptake and binding of drugs within the CNS.Curr Pharm Des. 2004;10(13):1493-503. doi: 10.2174/1381612043384736. Curr Pharm Des. 2004. PMID: 15134571 Review.
Cited by
-
Marked differences in the effect of antiepileptic and cytostatic drugs on the functionality of P-glycoprotein in human and rat brain capillary endothelial cell lines.Pharm Res. 2014 Jun;31(6):1588-604. doi: 10.1007/s11095-013-1264-4. Epub 2014 Jan 30. Pharm Res. 2014. PMID: 24477677
-
Reversal of multidrug resistance in leukemia cells using a transferrin-modified nanomicelle encapsulating both doxorubicin and psoralen.Aging (Albany NY). 2020 Apr 7;12(7):6018-6029. doi: 10.18632/aging.102992. Epub 2020 Apr 7. Aging (Albany NY). 2020. PMID: 32259795 Free PMC article.
-
A Role for P-Glycoprotein in Clearance of Alzheimer Amyloid β -Peptide from the Brain.Curr Alzheimer Res. 2016;13(6):615-20. doi: 10.2174/1567205013666160314151012. Curr Alzheimer Res. 2016. PMID: 26971931 Free PMC article.
-
Tailoring Lipid and Polymeric Nanoparticles as siRNA Carriers towards the Blood-Brain Barrier - from Targeting to Safe Administration.J Neuroimmune Pharmacol. 2017 Mar;12(1):107-119. doi: 10.1007/s11481-016-9685-6. Epub 2016 May 21. J Neuroimmune Pharmacol. 2017. PMID: 27209050
-
St. John's Wort constituents modulate P-glycoprotein transport activity at the blood-brain barrier.Pharm Res. 2010 May;27(5):811-22. doi: 10.1007/s11095-010-0074-1. Epub 2010 Mar 13. Pharm Res. 2010. PMID: 20229133
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
