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Cited by 119Drug Transport and Resistance MechanismsBarrier Structure and Function StudiesParkinson's Disease Mechanisms and Treatments

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Cellular localization of the organic cation transporters, OCT1 and OCT2, in brain microvessel endothelial cells and its implication for MPTP transport across the blood‐brain barrier and MPTP‐induced dopaminergic toxicity in rodents

Lin, Chun‐Jung, Tai, Ying, Huang, Miao‐Tzu, Tsai, Yuan‐Feen, Hsu, Hao‐Jui, Tzen, Kai‐Yuan, Liou, Horng‐Huei·2010·Journal of Neurochemistry
DOI 10.1111/j.1471-4159.2010.06801.x
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Abstract

The cellular localization of organic cation transporter (OCT) 1 and OCT2 in isolated brain microvessel endothelial cells from humans, rats, and mice and in cultured adult rat brain endothelial cells was examined by confocal microscopy and in isolated luminal and abluminal membrane fractions by Western blot analysis. Cellular uptake of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was measured with or without OCT1/OCT2 silencing. The interaction between MPTP and amantadine was studied by in vitro kinetic analysis and in vivo brain microdialysis. MPTP-induced dopaminergic toxicity was examined by measuring dopamine levels in the brain striatum and by positron emission tomography scanning. The results showed that both OCT1 and OCT2 were mainly expressed on the luminal side of brain microvessel endothelial cells and adult rat brain endothelial cells. Cellular uptake of MPTP was significantly (p < 0.05) decreased by about 53%, 60%, or 91% following silencing of OCT1, OCT2, or both, respectively. Amantadine competitively inhibited MPTP uptake in vitro and significantly (p < 0.05) reduced the area under the time-concentration curve for MPTP and MPP(+) in the brain extracellular fluid in rats and mice by 65-70% and 35-85%, respectively. MPTP-induced dopaminergic toxicity in mice was ameliorated by amantadine without stimulating dopamine turnover. In conclusion, OCT1 and OCT2 are important for MPTP transfer across the blood-brain barrier and amantadine reduces the blood-brain ba…

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  • OCT1/2 also transport N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin causing Parkinson's disease-like motor impairment.

    “OCT1/2 also transport N -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin causing PD-like motor impairment (363).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [363]

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Metadata

Authors
Lin, C., Tai, Y., Huang, M., Tsai, Y., Hsu, H., Tzen, K., & Liou, H.
Affiliations
  • National Taiwan University (TW)
  • National Taiwan University Hospital (TW)
Corresponding author
  • Lin, Chun‐Jung
  • Tzen, Kai‐Yuan
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2010-07-06
Volume
114
Issue
3
Pages
717-727
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/j.1471-4159.2010.06801.x
OpenAlex
W1486779292
Cited by
119
References
0
Citations by year
2026: 4 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 11 · 2021: 11 · 2020: 8 · 2019: 6 · 2018: 6 · 2017: 11 · 2016: 4 · 2015: 11 · 2014: 7 · 2013: 6 · 2012: 10
FWCI
4.27
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Council
  • National Taiwan University
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
organic cation transporters, OCT1, OCT2, MPTP, blood-brain barrier, brain microvascular endothelial cells, amantadine, MPP+, Parkinson's disease
MeSH terms
Organic Cation Transporter 2, Animals, Binding, Competitive, Biological Transport, Active, Blood-Brain Barrier, Capillaries, Cells, Cultured, Dopamine, Humans, Male, Mice, Inbred C57BL, Neurotoxins, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Rats, Wistar, Parkinsonian Disorders, Organic Cation Transport Proteins, Endothelial Cells, Octamer Transcription Factor-1, Mice, Rats

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