Inhibition of the norepinephrine transporter function in cultured bovine adrenal medullary cells by bisphenol A

We report here the effects of an environmental estrogen, bisphenol A, on norepinephrine (NE) transporter function in cultured bovine adrenal medullary cells. The effects of bisphenol A were compared to those of 17β-estradiol. Bisphenol A significantly inhibited [ 3 H ]NE uptake by the cells in a concentration-dependent manner (1–100 μM). Kinetic analysis revealed that bisphenol A, as well as 17β-estradiol, noncompetitively inhibited [ 3 H ]NE uptake. Bisphenol A and 17β-estradiol inhibited the specific binding of [ 3 H ]desipramine to plasma membranes isolated from bovine adrenal medulla. As shown by Scatchard analysis of [ 3 H ]desipramine binding, bisphenol A increased the dissociation constant ( K d ) and decreased the maximal binding ( B max), indicating a mixed type of inhibition. 17β-Estradiol increased the K d without altering the B max, thereby indicating competitive inhibition. The present findings suggest that bisphenol A inhibits the function of the NE transporter by acting on a site different from that of 17β-estradiol in the adrenal medulla and probably in the brain noradrenergic neurons.