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 (ω‐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′‐(β‐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.