Potentiation of the Human GABAA Receptor As a Novel Mode of Action of Lower-Chlorinated Non-Dioxin-Like PCBs

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• 作者：Elsa C. Antunes Fernandes ; Hester S. Hendriks ; Regina G. D. M. van Kleef ; Martin van den Berg ; Remco H. S. Westerink
• 刊名：Environmental Science & Technology
• 出版年：2010
• 出版时间：April 15, 2010
• 年：2010
• 卷：44
• 期：8
• 页码：2864-2869
• 全文大小：171K
• 年卷期：v.44,no.8(April 15, 2010)
• ISSN：1520-5851

文摘

PCBs are still ubiquitous pollutants despite the ban on their industrial and commercial use. To date, risk characterization and assessment of non-dioxin-like PCBs (NDL-PCBs), especially with respect to neurotoxicity, is hampered by a lack of data. Therefore, the effects of six common NDL congeners (PCB28, 52, 101, 138, 153 and 180) on human GABA_A receptors, expressed in Xenopus oocytes, were investigated using the two-electrode voltage-clamp technique. When coapplied with GABA (at EC₂₀), PCB28 and PCB52 concentration-dependently potentiate the GABA_A receptor-mediated ion current. Though the LOEC for both PCB28 and PCB52 is 0.3 μM, PCB28 is more potent than PCB52 (maximum potentiation at 10 μM amounting to 98.3 ± 12.5% and 25.5 ± 1.4%, respectively). Importantly, coapplication of PCB28 (0.3 μM) and PCB52 (10 μM) resulted in an apparently additive potentiation of the GABA_A response, whereas coapplication of PCB28 (0.3 μM) and PCB153 (10 μM) attenuated the PCB28-induced potentiation. The present results suggest that the potentiation of human GABA_A receptor function is specific for lower-chlorinated NDL-PCBs and that higher molecular weight PCBs may attenuate this potentiation as a result of competitive binding to human GABA_A receptors. Nonetheless, this novel mode of action could (partly) underlie the previously recognized NDL-PCB-induced neurobehavioral alterations.