Carrier-mediated processes in blood-brain barrier penetration and neural uptake of paraquat

K. Shimizu, K. Ohtaki, K. Matsubara, K. Aoyama, T. Uezono, O. Saito, Manabu Suno, K. Ogawa, N. Hayase, K. Kimura, H. Shiono

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

Due to the structural similarity to N-methyl-4-phenyl pyridinium (MPP+), paraquat might induce dopaminergic toxicity in the brain. However, its blood-brain barrier (BBB) penetration has not been well documented. We studied the manner of BBB penetration and neural cell uptake of paraquat using a brain microdialysis technique with HPLC/UV detection in rats. After subcutaneous administration, paraquat appeared dose-dependently in the dialysate. In contrast, MPP+ could not penetrate the BBB in either control or paraquat pre-treated rats. These data indicated that the penetration of paraquat into the brain would be mediated by a specific carrier process, not resulting from the destruction of BBB function by paraquat itself or a paraquat radical. To examine whether paraquat was carried across the BBB by a certain amino acid transporter, L-valine or L-lysine was pre-administered as a co-substrate. The pre-treatment of L-valine, which is a high affinity substrate for the neutral amino acid transporter, markedly reduced the BBB penetration of paraquat. When paraquat was administered to the striatum through a microdialysis probe, a significant amount of paraquat was detected in the striatal cells after a sequential 180-min washout with Ringer's solution. This uptake was significantly inhibited by a low Na+ condition, but not by treatment with putrescine, a potent uptake inhibitor of paraquat into lung tissue. These findings indicated that paraquat is possibly taken up into the brain by the neutral amino acid transport system, then transported into striatal, possibly neuronal, cells in a Na+-dependent manner.

Original languageEnglish
Pages (from-to)135-142
Number of pages8
JournalBrain Research
Volume906
Issue number1-2
DOIs
Publication statusPublished - Jul 6 2001
Externally publishedYes

Fingerprint

Paraquat
Blood-Brain Barrier
Neutral Amino Acid Transport Systems
Corpus Striatum
Microdialysis
Brain
Valine
Amino Acid Transport Systems
Putrescine
Dialysis Solutions
Lysine
High Pressure Liquid Chromatography

Keywords

  • Amino acid transporter
  • Blood-brain barrier
  • Brain microdialysis
  • Paraquat
  • Sodium-dependent uptake

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Shimizu, K., Ohtaki, K., Matsubara, K., Aoyama, K., Uezono, T., Saito, O., ... Shiono, H. (2001). Carrier-mediated processes in blood-brain barrier penetration and neural uptake of paraquat. Brain Research, 906(1-2), 135-142. https://doi.org/10.1016/S0006-8993(01)02577-X

Carrier-mediated processes in blood-brain barrier penetration and neural uptake of paraquat. / Shimizu, K.; Ohtaki, K.; Matsubara, K.; Aoyama, K.; Uezono, T.; Saito, O.; Suno, Manabu; Ogawa, K.; Hayase, N.; Kimura, K.; Shiono, H.

In: Brain Research, Vol. 906, No. 1-2, 06.07.2001, p. 135-142.

Research output: Contribution to journalArticle

Shimizu, K, Ohtaki, K, Matsubara, K, Aoyama, K, Uezono, T, Saito, O, Suno, M, Ogawa, K, Hayase, N, Kimura, K & Shiono, H 2001, 'Carrier-mediated processes in blood-brain barrier penetration and neural uptake of paraquat', Brain Research, vol. 906, no. 1-2, pp. 135-142. https://doi.org/10.1016/S0006-8993(01)02577-X
Shimizu K, Ohtaki K, Matsubara K, Aoyama K, Uezono T, Saito O et al. Carrier-mediated processes in blood-brain barrier penetration and neural uptake of paraquat. Brain Research. 2001 Jul 6;906(1-2):135-142. https://doi.org/10.1016/S0006-8993(01)02577-X
Shimizu, K. ; Ohtaki, K. ; Matsubara, K. ; Aoyama, K. ; Uezono, T. ; Saito, O. ; Suno, Manabu ; Ogawa, K. ; Hayase, N. ; Kimura, K. ; Shiono, H. / Carrier-mediated processes in blood-brain barrier penetration and neural uptake of paraquat. In: Brain Research. 2001 ; Vol. 906, No. 1-2. pp. 135-142.
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