Non-genomic modulation of dopamine release by bisphenol-A in PC12 cells.
An endocrine disruptor chemical, bisphenol-A (BPA), is reported to have several short-term actions in various tissues and/or cells; however, the mechanisms of these actions have not been fully elucidated. We investigated short-term actions evoked by BPA in pheochromocytoma PC12 cells. BPA elicited dopamine release in PC12 cells in a dose-dependent manner. A selective N-type calcium channel antagonist (omega-conotoxin GVIA) and a ryanodine receptor blocker (ryanodine) inhibited the BPA-induced dopamine release. The expression of ryanodine receptor mRNA was detected by RT-PCR in PC12 cells. Subsequently, in order to prove whether membrane receptors participate in BPA-evoked dopamine release, a guanine nucleotide-binding protein inhibitor [guanosine 5'-(beta-thio) diphosphate], cyclic AMP antagonist (Rp-cAMPS) or protein kinase A inhibitor (H7 or H89) was added to PC12 cells prior to BPA-treatment. All of these agents suppressed BPA-evoked dopamine release, indicating that multiple signaling pathways may be involved in BPA-evoked dopamine release in PC12 cells. In conclusion, we demonstrated that BPA induced dopamine release in a non-genomic manner through guanine nucleotide-binding protein and N-type calcium channels. These findings illustrate a novel function of BPA and suggest that exposure to BPA influences the function of dopaminergic neurons.
Yoneda
Takashi
T
Department of Chemical Biology, Osaka City University Medical School, Osaka, Japan.
Hiroi
Toyoko
T
Osada
Mayuko
M
Asada
Akira
A
Funae
Yoshihiko
Y
D000818:Animals; D001559:Benzhydryl Compounds; D015152:Blotting, Northern; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D008954:Models, Biological; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012428:Ruthenium / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D002121:Calcium Channel Blockers; D000242:Cyclic AMP; D004298:Dopamine; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D006153:Guanosine Diphosphate; D008996:Monoamine Oxidase Inhibitors; D010636:Phenols; D012333:RNA, Messenger; D012428:Ruthenium; D019837:Ryanodine Receptor Calcium Release Channel; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; C023427:guanosine 5'-O-(2-thiodiphosphate); C006780:bisphenol A; D000098826:Bisphenol A Compounds