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

• Published in: Biochemical pharmacology 2003-06, Vol.65 (12), p.2049-2054
• Main Authors: Toyohira, Yumiko, Utsunomiya, Kensuke, Ueno, Susumu, Minami, Kouichiro, Uezono, Yasuhito, Yoshimura, Reiji, Tsutsui, Masato, Izumi, Futoshi, Yanagihara, Nobuyuki
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Adrenal Medulla - cytology; Adrenal Medulla - drug effects; Adrenal Medulla - metabolism; Adrenal medullary cells; Animals; Benzhydryl Compounds; Biological and medical sciences; Biological Transport - drug effects; Bisphenol A; Cattle; Cell Membrane - drug effects; Cell Membrane - metabolism; Cells, Cultured; Desipramine - metabolism; Environmental estrogens; Estradiol - pharmacology; Estrogens - pharmacology; Estrogens, Non-Steroidal - pharmacology; Medical sciences; Norepinephrine - metabolism; Norepinephrine Plasma Membrane Transport Proteins; Norepinephrine transporter; Norepinephrine uptake; Phenols - pharmacology; Symporters - metabolism; Tritium
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(03)00159-X

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.