Staff Publications

Staff Publications

  • external user (warningwarning)
  • Log in as
  • language uk
  • About

    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

    We have a manual that explains all the features 

Record number 486172
Title PCB-47, PBDE-47, and 6-OH-PBDE-47 Differentially Modulate Human GABAA and a4b2 Nicotinic Acetylcholine Receptors
Author(s) Hendriks, H.S.; Antunes Fernandes, E.C.; Bergman, A.; Berg, M. van den; Westerink, R.H.S.
Source Toxicological sciences 118 (2010)2. - ISSN 1096-6080 - p. 635 - 642.
Department(s) Food Quality and Design
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2010
Keyword(s) polybrominated diphenyl ethers - brominated flame-retardant - neonatal brain-development - long-term potentiation - polychlorinated-biphenyls - adult mice - spontaneous behavior - perinatal exposure - hippocampus - metabolites
Abstract Polychlorinated biphenyls (PCBs) and the structurally related polybrominated diphenyl ethers (PBDEs) are abundant persistent organic pollutants that exert several comparable neurotoxic effects. Importantly, hydroxylated metabolites of PCBs and PBDEs have an increased neurotoxic potency. Recently, we demonstrated that PCBs can act as (partial) agonist on GABAA neurotransmitter receptors, with PCB-47 being the most potent congener. It is, however, unknown whether PBDE-47 and its metabolite 6-OH-PBDE-47 exert similar effects and if these effects are limited to GABAA receptors only. We therefore investigated effects of PCB-47, PBDE-47, and 6-OH-PBDE-47 on the inhibitory GABAA and excitatory a4b2 nicotinic acetylcholine (nACh) receptor expressed in Xenopus oocytes using the twoelectrode voltage-clamp technique. Since human exposure is generally not limited to individual compounds, experiments with binary mixtures were also performed. The results demonstrate that PCB-47 and 6-OH-PBDE-47 act as full and partial agonist on the GABAA receptor. However, both congeners act as antagonist on the nACh receptor. PBDE-47 does not affect either type of receptor. Binary mixtures of PCB-47 and 6-OH-PBDE-47 induced an additive activation as well as potentiation of GABAA receptors, whereas this mixture resulted in an additive inhibition of nACh receptors. Binary mixtures of PBDE-47 and 6-OH-PBDE-47 yielded similar effects as 6-OH-PBDE-47 alone. These findings demonstrate that GABAA and nACh receptors are affected differently by PCB-47 and 6-OH-PBDE-47, with inhibitory GABAA-mediated signaling being potentiated and excitatory a4b2 nACh–mediated signaling being inhibited. Considering these opposite actions and the additive interaction of the congeners, these effects are likely to be augmented in vivo.
Comments
There are no comments yet. You can post the first one!
Post a comment
 
Please log in to use this service. Login as Wageningen University & Research user or guest user in upper right hand corner of this page.