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Cited by 304Amino Acid Enzymes and MetabolismBarrier Structure and Function StudiesDrug Transport and Resistance Mechanisms

The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.

The 4F2hc/LAT1 complex transports l-DOPA across the blood–brain barrier

Kageyama, Takashi, Nakamura, Masaru, Matsuo, Akinori, Yamasaki, Yasuomi, Takakura, Yoshinobu, Hashida, Mitsuru, Kanai, Yoshikatsu, Naito, Mikihiko, Tsuruo, Takashi, Minato, Nagahiro, Shimohama, Shun·2000·Brain Research
DOI 10.1016/s0006-8993(00)02758-x
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Abstract

L-DOPA is transported across the blood-brain barrier (BBB) by an amino acid transporter, system L. Recently, it has been demonstrated that system L consists of two subunits, 4F2hc and either LAT1 or LAT2. 4F2hc/LAT1 and 4F2hc/LAT2 show different transport characteristics, while their distribution in the brain has not been determined. To clarify whether 4F2hc/LAT1 participates in L-DOPA transport across the BBB, we first examined the expression of 4F2hc/LAT1 in the mouse brain capillary endothelial cell line, MBEC4, as an in vitro BBB model. Northern hybridization and immunoblotting revealed that both 4F2hc and LAT1 are expressed and form a heterodimer in MBEC4 cells. To confirm whether 4F2hc/LAT1 acts as system L to transport L-DOPA, we characterized L-DOPA uptake into the cells. The uptake process was time-dependent, temperature-sensitive, and Na(+)-independent. Neutral amino acids with bulky side chains and a bicyclic amino acid, 2-aminobicyclo-[2, 2,1]-heptane-2-carboxylic acid (BCH), inhibited L-DOPA uptake into MBEC4 cells to a great extent, while an acidic amino acid, basic amino acids, and glycine had no effect. Other neutral amino acids, such as alanine, asparagine, glutamine, serine, and threonine inhibited L-DOPA uptake by 40-70% at most. These characteristics are more compatible with those of 4F2hc/LAT1, rather than those of 4F2hc/LAT2. Finally, immunohistochemistry with anti-LAT1 antibody demonstrated that LAT1 is predominantly expressed in the microvessels of the…

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Metadata

Authors
Kageyama, T., Nakamura, M., Matsuo, A., Yamasaki, Y., Takakura, Y., Hashida, M., Kanai, Y., Naito, M., Tsuruo, T., Minato, N., & Shimohama, S.
Affiliations
  • Kyoto University (JP)
  • Kyorin University (JP)
  • Institute for Quantitative Biosciences, The University of Tokyo (JP)
Corresponding author
Shimohama, Shun
ORCID
Venue
Brain Research
Publisher
Elsevier BV
Published
2000-10
Volume
879
Issue
1-2
Pages
115-121
ISSN
0006-8993 (ISSN-L)
DOI
10.1016/s0006-8993(00)02758-x
OpenAlex
W2152525754
Cited by
298
References
37
Citations by year
2026: 13 · 2025: 16 · 2024: 12 · 2023: 18 · 2022: 28 · 2021: 17 · 2020: 19 · 2019: 15 · 2018: 17 · 2017: 13 · 2016: 12 · 2015: 9 · 2014: 10 · 2013: 15 · 2012: 7
FWCI
3.83
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Brain Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
Ministry of Education, Culture, Sports, Science and Technology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
blood-brain barrier, LAT1, LAT2, system L amino acid transporter, amino acid transport, 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid
MeSH terms
Amino Acids, Animals, Biological Transport, Blood-Brain Barrier, Brain, Capillaries, Carrier Proteins, Cell Line, Cerebrovascular Circulation, Endothelium, Vascular, Female, Levodopa, Male, Mice, Inbred BALB C, Recombinant Proteins, Antigens, CD, Protein Subunits, Amino Acid Transport Systems, Fusion Regulatory Protein-1, Mice

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