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ABC Transporters at the Blood–Brain Barrier

  • David S. Miller
Chapter
Part of the Topics in Medicinal Chemistry book series (TMC, volume 10)

Abstract

In the blood–brain barrier several ABC transporters are expressed at the luminal, blood-facing, plasma membrane of the brain capillary endothelial cells. There they function as ATP-driven efflux pumps for xenobiotics and endogenous metabolites, thus providing an important element of the barrier. When these transporters limit neurotoxicant entry into the CNS, they are neuroprotective; when they limit therapeutic drug entry, they become major obstacles to drug delivery to treat CNS diseases. Here I review function and regulation of ABC transporters at the blood–brain barrier, with an emphasis on recently disclosed mechanisms that alter transporter expression and transport activity.

Keywords

BCRP Blood–brain barrier Brain capillary endothelium Disease Drug delivery MRP P-glycoprotein Regulation 

Abbreviations

ABC

ATP-binding cassette

AD

Alzheimer’s disease

AEDs

Antiepileptic drugs

AhR

Arylhydrocarbon receptor

Akt

Protein kinase B

ApoE

Apolipoprotein E

BCRP

Breast cancer resistance protein (ABCG2)

BSEP

Bile salt export pump

CAR

Constitutive androstane receptor

CFTR

Cystic fibrosis transmembrane regulator (ABCC7)

CNS

Central nervous system

COX-2

Cyclo-oxygenase-2

E2

17-β-estradiol

EP-1

Prostaglandin E2 receptor

ER

Estrogen receptor

FXR

Farnesyl-X receptor

GSK-3β

Glycogen synthase kinase 3 beta

hAPP

Human amyloid precursor protein

iNOS

Inducible nitric oxide synthase

JNK

c-Jun N-terminal kinase

LXR

Liver-X receptor

MRP

Multidrug resistance-associated protein

NF-κB

Nuclear factor kappa-light-chain-enhancer of activated B cells

NMDA

N-methyl-d-aspartate

PCBs

Polychlorinated biphenyls

PCN

Pregnenolone-16-alpha-carbonitrile

PCR

Polymerase chain reaction

PI3-K

Phosphatidylinositide 3-kinase

PK

Pharmacokinetics

PKCβ1

Protein kinase C isoform β1

PTEN

Phosphatase and tensin homolog

PXR

Pregnane-X receptor

S1P

Sphingosine-1-phosphate

S1PR1

Sphingosine-1-phosphate receptor 1

TNF-α

Tumor necrosis factor-α

VDR

Vitamin D receptor

VEGF

Vascular endothelial growth factor

Notes

Acknowledgements

This work was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. I thank all the past and present members of my laboratory for their hard work and creativity.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • David S. Miller
    • 1
  1. 1.Laboratory of Toxicology and PharmacologyNIH/NIEHSResearch Triangle ParkUSA

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