Angus W G, Contreras M L
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824, USA.
Toxicol Lett. 1996 Dec 31;89(3):191-9. doi: 10.1016/s0378-4274(96)03810-6.
In PC12 cells, Aroclor 1254 produced a concentration-dependent decrease in basal and K(+)-evoked dopamine (DA) release, and cellular DA levels. Aroclor 1254 did not alter the fraction of cellular DA released, suggesting that the decreased release of DA was solely due to decreased cellular levels of DA, and not to decreased packaging of DA or inhibition of neurotransmitter release. The coplanar congener 3,3',4,4',5-pentachlorobiphenyl decreased cellular DA levels and release of DA at levels that produced cytotoxicity. Absent of any apparent cytotoxicity, the ortho-substituted PCB congeners 2,2',5,5'-tetrachlorobiphenyl, 2,2',3,3',4,4'-hexachlorobiphenyl, 2,3',4,4',5-pentachlorobiphenyl, and 2,2',4,4',5,5'-hexachlorobiphenyl were effective in decreasing the amount of DA released from PC12 cells. These results suggest that ortho-chlorinated PCBs can cause decreased K(+)-evoked DA release through non-Ah receptor-mediated mechanisms. Furthermore, the PCB-mediated decrease in DA release was not due to impairment of DA packaging or release, but only due to decreased cellular DA levels.
在PC12细胞中，艾氏剂1254使基础状态下以及钾离子诱发的多巴胺（DA）释放量和细胞内DA水平呈浓度依赖性降低。艾氏剂1254并未改变细胞内释放的DA比例，这表明DA释放量的减少完全是由于细胞内DA水平降低，而非DA包装减少或神经递质释放受到抑制。共平面同系物3,3',4,4',5-五氯联苯在产生细胞毒性的水平下降低了细胞内DA水平和DA释放量。在没有任何明显细胞毒性的情况下，邻位取代的多氯联苯同系物2,2',5,5'-四氯联苯、2,2',3,3',4,4'-六氯联苯、2,3',4,4',5-五氯联苯和2,2',4,4',5,5'-六氯联苯均能有效降低PC12细胞释放的DA量。这些结果表明，邻位氯化多氯联苯可通过非芳烃受体介导的机制导致钾离子诱发的DA释放减少。此外，多氯联苯介导的DA释放减少并非由于DA包装或释放受损，而仅仅是由于细胞内DA水平降低。
