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The Blood Brain Barrier (BBB) pp 49–69Cite as

ABC Transporters at the Blood–Brain Barrier

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Part of the book series: Topics in Medicinal Chemistry ((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.

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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

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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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Authors and Affiliations

  1. Laboratory of Toxicology and Pharmacology, NIH/NIEHS, Research Triangle Park, NC, 27709, USA

    David S. Miller

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Editors and Affiliations

  1. Institut für Pharmazie und Molekulare Biotechnologie, Universität Heidelberg, Heidelberg, Baden-Württemberg, Germany

    Gert Fricker

  2. Dept. for Pharmaceutical Technology and Pharmacology, Institute für Pharmacy and Molecular Biotechnology, Heidelberg, Germany

    Melanie Ott

  3. Dept. for Pharmaceutical Technology and Pharmacology, Institute für Pharmacy and Molecular Biotechnology, Heidelberg, Germany

    Anne Mahringer

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Miller, D.S. (2013). ABC Transporters at the Blood–Brain Barrier. In: Fricker, G., Ott, M., Mahringer, A. (eds) The Blood Brain Barrier (BBB). Topics in Medicinal Chemistry, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7355_2013_31

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