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Effect of polychlorinated biphenyls on the uptake of dopamine into rat brain synaptic vesicles: a structure-activity study.

Abstract：

:PCBs are neurotoxic compounds that have a known effect on the dopaminergic system in the brain. In a previous work it was established that PCBs are potent inhibitors of the uptake of dopamine into rat brain synaptic vesicles. In this work we further investigated the vesicular dopamine uptake in response to different PCBs to explore the structure-activity relationship involved in this effect. Twenty PCB congeners were selected, based on multivariate chemical characterization, to cover the chemical variation within tetra- to hepta-chlorinated PCBs. PCBs of large structural variation were tested and the general finding was that only the ortho-substituted PCBs inhibited the dopamine uptake. The most active congeners were the penta- and hexa-chlorinated PCBs. Furthermore, the uptake was correlated with parameters describing the absolute hardness, the octanol-water partition coefficient, and the Henry's law constant. These parameters are correlated to the number of chlorine atoms in ortho positions and to the size of the molecule. Notably the most active PCBs are highly prevalent in the environment and are disposed to bioaccumulate in wildlife. Thus, these neurotoxic effects should be included in the risk assessment of PCBs.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Mariussen E,Andersson PL,Tysklind M,Fonnum F

doi

10.1006/taap.2001.9231

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

176-83

issue

2

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(01)99231-2

journal_volume

175

pub_type

杂志文章

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