Rapid Ca(2+) signaling induced by Bisphenol A in cultured rat hippocampal neurons.
OBJECTIVE
Bisphenol A (BPA) is a typical endocrine disrupter. We investigated the mechanisms of rapid Ca(2+) signaling induced by a low dose BPA application in cultured hippocampal neurons.


METHODS
The primary culture of hippocampal neurons were prepared from postnatal 3 to 5-day-old rats. Cells were loaded with Calcium Green-1 fluorophore. Ca(2+) imaging and analysis were performed by Argus system.


RESULTS
The application of BPA at 10-100 nM induced a transient increase in the intracellular Ca(2+) of N-methyl-D-aspartate (NMDA)-responsive neurons. The Ca(2+) transient occurred within 30 sec after the BPA application. The proportion of BPA-responsive neurons was 9.6 % and 8.5 % of the total NMDA-responsive neurons, respectively, upon 10 nM and 100 nM BPA application. The pre-treatment of neurons with Ca(2+) channel blockers, thapsigargin and nifedipine, considerably decreased the proportion of BPA-responsive neurons to 0.7 % and 3.7%, respectively. The treatment of neurons with an antagonist of estrogen receptor, ICI 182,780, also significantly decreased the proportion of BPA-responsive neurons down to 1.1 %.


CONCLUSIONS
These results suggest that a low dose BPA application rapidly drives the Ca(2+) signaling system via activation of non-genomic pathway including estrogen receptors.
Tanabe
Nobuaki
N
Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of Tokyo at Komaba, Meguro, Tokyo 153-8902, Japan.
Kimoto
Tetsuya
T
Kawato
Suguru
S
D000818:Animals; D001559:Benzhydryl Compounds; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005456:Fluorescent Dyes; D000077267:Fulvestrant; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D016202:N-Methylaspartate / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D002118:Calcium; D002121:Calcium Channel Blockers; D004958:Estradiol; D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D018690:Excitatory Amino Acid Agonists; D005456:Fluorescent Dyes; D000077267:Fulvestrant; D016202:N-Methylaspartate; D010636:Phenols; D011960:Receptors, Estrogen; C006780:bisphenol A; D000098826:Bisphenol A Compounds