Nongenomic Inhibition of Catecholamine Secretion by 17β‐Estradiol in PC12 Cells

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Abstract
We investigated the effects of 17β‐estradiol, an estrogen, on [3H]norepinephrine ([3H]NE) secretion in PC12 cells. Pretreatment with 17β‐estradiol reduced 70 mM K+‐induced [3H]NE secretion in a concentration‐dependent manner with a half‐maximal inhibitory concentration (IC50) of 2 ± 1 μM. The 70 mM K+‐induced cytosolic free Ca2+ concentration ([Ca2+]i) rise was also reduced when the cells were treated with 17β‐estradiol (IC50 = 15 ± 2 μM). Studies with voltage‐sensitive calcium channel (VSCC) antagonists such as nifedipine and ω‐conotoxin GVIA revealed that both L‐ and N‐type VSCCs were affected by 17β‐estradiol treatment. The 17β‐estradiol effect was not changed by pretreatment of the cells with actinomycin D and cycloheximide for 5 h. In addition, treatment with pertussis or cholera toxin did not affect the inhibitory effect of 17β‐estradiol. 17β‐Estradiol also inhibited the ATP‐induced [3H]NE secretion and [Ca2+]i rise. In PC12 cells, the ATP‐induced [Ca2+]i rise is known to occur through P2X2 receptors, the P2Y2‐mediated phospholipase C (PLC) pathway, and VSCCs. 17β‐Estradiol pretreatment during complete inhibition of the PLC pathway and VSCCs inhibited the ATP‐induced [Ca2+]i rise. Our results suggest that 17β‐estradiol inhibits catecholamine secretion by inhibiting L‐ and N‐type Ca2+ channels and P2X2 receptors in a nongenomic manner.