Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Trends Pharmacol Sci. 2010 Jun;31(6):246-54. doi: 10.1016/j.tips.2010.03.003. Epub 2010 Apr 24.

Regulation of P-glycoprotein and other ABC drug transporters at the blood-brain barrier.

Author information

  • Laboratory of Toxicology and Pharmacology, NIH/NIEHS, P.O. Box 12233, Research Triangle Park, NC 27709, USA. miller@niehs.nih.gov <miller@niehs.nih.gov>

Abstract

ATP-binding cassette (ABC) transporters are important selective elements of the blood-brain barrier. They line the luminal plasma membrane of the brain capillary endothelium, facing the vascular space, and both protect the central nervous system from entry of neurotoxicants and limit the access of therapeutic drugs to the brain parenchyma. Recent studies highlight the multiple signaling pathways through which the expression and activity of P-glycoprotein and other ABC transporters are modulated in response to xenobiotics, stress and disease. The results show that increased transporter expression occurs in response to signals that activate specific transcription factors, including pregnane-X receptor, constitutive androstane receptor, nuclear factor-kappaB and activator protein-1, and that reduced transporter activity occurs rapidly and reversibly in response to signaling through Src kinase, protein kinase C and estrogen receptors. A detailed understanding of such regulation can provide the basis for improved neuroprotection and enhanced therapeutic drug delivery to the brain.

PMID:
20417575
[PubMed - indexed for MEDLINE]
PMCID:
PMC2882496
Free PMC Article

Images from this publication.See all images (2)Free text

Figure 1
Figure 2
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk