Effects of polychlorinated biphenyls on dopamine release from PC12 cells.
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.
Angus
W G
WG
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824, USA.
Contreras
M L
ML
D000818:Animals; D001140:Aroclors / Q000633:toxicity*; D002478:Cells, Cultured; D020111:Chlorodiphenyl (54% Chlorine); D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016716:PC12 Cells / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D013997:Time Factors
D001140:Aroclors; D020111:Chlorodiphenyl (54% Chlorine); D011078:Polychlorinated Biphenyls; D004298:Dopamine