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Drug Delivery to the Brain pp 23–62Cite as

Recent Progress in Blood–Brain Barrier and Blood–CSF Barrier Transport Research: Pharmaceutical Relevance for Drug Delivery to the Brain

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Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 10))

Abstract

The blood–brain barrier (BBB) and the blood–CSF barrier (BCSFB) possess multiple transport systems for endogenous and xenobiotic compounds to maintain functional homeostasis in the central nervous system (CNS). Accumulating evidence on the transport systems has provided a basis for the development of rational strategies for drug delivery and targeting to CNS. The blood-to-brain influx transport systems at the BBB have a great potential for CNS-acting drug delivery and targeting to the brain. The brain-to-blood efflux transport systems at the BBB including ATP-binding cassette transporters hinder the drug penetration to the brain. Efflux transport systems at the BBB and BCSFB also play an important role in cerebral clearance of endogenous neurotoxic compounds which are associated with disorders of the CNS. Several drugs influence the endogenous clearance system at the brain barriers. This chapter focuses on the current state of knowledge concerning the roles of transport systems for endogenous and xenobiotic compounds at the BBB and the BCSFB, and the potential implications of these systems for CNS drug delivery.

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Abbreviations

ABC:

ATP-binding cassette

Aβ:

Amyloid-β peptide

AD:

Alzheimer’s disease

α2M:

α2-macrogloblin

AMA:

Amantadine

ANP:

Atrial natriuretic peptide

Apo:

Apolipoprotein

Asct:

Alanine-serine-cysteine transporter

Ata:

Amino acid transporter

ATB0,+ :

Amino acid transporter B0,+

BBB:

Blood–brain barrier

BCSFB:

Blood–cerebrospinal fluid barrier

BCRP:

Breast cancer-resistance protein

Cat:

Cationic amino acid transporter

Cht:

Choline transporter

Cnt:

Concentrative nucleoside transporter

CNS:

Central nervous system

Crt:

Creatine transporter

Ctl:

Choline transporter-like protein

DHEAS:

Dehydroepiandrosterone sulfate

DPDPE:

[D-penicillamine2,5]encephalin

Eaat:

Excitatory amino acid transporter

ENT:

Equilibrative nucleoside transporter

4F2hc:

Heavy chain of the 4F2 cell-surface antigen

GABA:

γ-Aminobutyric acid

GAMT:

S-Adenosylmethionine:guanidinoacetate N-methyltransferase

Gat:

γ-Aminobutyric acid transporter

GLUT:

Glucose transporter

GC:

Guanidino compound

GlySar:

Glycylsarcosine

hCMEC/D3:

Human capillary endothelial cell line

HDL:

High-density lipoprotein

HVA:

Homovanillic acid

IS:

Indoxyl sulfate

LAT/Lat:

L-type amino acid transporter

LRP:

Low-density lipoprotein receptor-related protein

Mate:

Multidrug and toxin extrusion transporter

MCT/Mct:

Monocarboxylic acid transporter

MDR:

Multidrug-resistance protein

6-MP:

6-Mercaptopurine

MPP+ :

1-Methyl-4-phenylpyridinium

MRP/Mrp:

Multidrug-resistance-associated protein

mTOR:

Mammalian target of rapamycin

Npr-C:

Natriuretic peptide receptor C

NSAID:

Nonsteroidal anti-inflammatory drug

Oat:

Organic anion transporter

OATP/Oatp:

Organic anion transporting polypeptide

Oct:

Organic cation transporter

Octn:

Organic cation/carnitine transporters

PAO:

Phenylarsine oxide

Pept:

Proton-coupled oligopeptide transporter

PGE2 :

Prostaglandin E2

P-gp:

P-glycoprotein

Pmat:

Plasma membrane monoamine transporter

RIM:

Rimantadine

Taut:

Taurine transporter

TCDD:

2,3,7,8-Tetrachlorodibenzo-p-dioxin

PPx:

Pharmacoproteomics

SLC:

Solute carrier

6-TG:

6-Thioguanine

TR-BBB:

Rat conditionally immortalized brain capillary endothelial cell line

TR-CSFB:

Conditionally immortalized choroid plexus epithelial cell line

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Acknowledgement

We would like to acknowledge the collaboration of Drs. K. Hosoya and S. Akanuma (University of Toyama). This work was supported, in part, by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai, Japan

    Masanori Tachikawa, Yasuo Uchida & Tetsuya Terasaki Ph.D.

  2. Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Sumio Ohtsuki

Authors
  1. Masanori Tachikawa
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  2. Yasuo Uchida
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  3. Sumio Ohtsuki
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  4. Tetsuya Terasaki Ph.D.
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Corresponding author

Correspondence to Tetsuya Terasaki Ph.D. .

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Editors and Affiliations

  1. Pharmaceutical Biosciences, Uppsala University Pharmacokinetics and Drug Therapy, Uppsala, Sweden

    Margareta Hammarlund-Udenaes

  2. LACDR/Pharmacology, Leiden University, Leiden, The Netherlands

    Elizabeth C.M. de Lange

  3. Pharmaceutical Sciences Division, University of Wisconsin-Madison School of Pharmacy, Madison, Wisconsin, USA

    Robert G. Thorne

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© 2014 American Association of Pharmaceutical Scientists

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Tachikawa, M., Uchida, Y., Ohtsuki, S., Terasaki, T. (2014). Recent Progress in Blood–Brain Barrier and Blood–CSF Barrier Transport Research: Pharmaceutical Relevance for Drug Delivery to the Brain. In: Hammarlund-Udenaes, M., de Lange, E., Thorne, R. (eds) Drug Delivery to the Brain. AAPS Advances in the Pharmaceutical Sciences Series, vol 10. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9105-7_2

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