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

Citation
K. Shimizu et al., Carrier-mediated processes in blood-brain barrier penetration and neural uptake of paraquat, BRAIN RES, 906(1-2), 2001, pp. 135-142
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
BRAIN RESEARCH
ISSN journal
0006-8993 → ACNP
Volume
906
Issue
1-2
Year of publication
2001
Pages
135 - 142
Database
ISI
SICI code
0006-8993(20010706)906:1-2<135:CPIBBP>2.0.ZU;2-U
Abstract
Due to the structural similarity to N-methyl- 4-phenyl pyridinium (MPP+), p araquat might induce dopaminergic toxicity in the brain. However, its blood -brain barrier (BBB) penetration has not been well documented. We studied t he manner of BBB penetration and neural cell uptake of paraquat using a bra in microdialysis technique with HPLC/UV detection in rats. After subcutaneo us administration, paraquat appeared dose-dependently in the dialysate. In contrast, MPP+ could not penetrate the BBB in either control or paraquat pr e-treated rats. These data indicated that the penetration of paraquat into the brain would be mediated by a specific carrier process, not resulting fr om 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-substr ate. 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 microdi alysis probe, a significant amount of paraquat was detected in the striatal cells after a sequential 180-min washout with Ringer's solution. This upta ke was significantly inhibited by a low Na+ condition, but not by treatment with putrescine, a potent uptake inhibitor of paraquat into lung tissue. T hese findings indicated that paraquat is possibly taken up into the brain b y the neutral amino acid transport system, then transported into striatal, possibly neuronal, cells in a Na+-dependent manner. (C) 2001 Elsevier Scien ce B.V. All rights reserved.