title: Inhibition of the norepinephrine transporter function in cultured bovine adrenal medullary cells by bisphenol A.
abstract: 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 17beta-estradiol. Bisphenol A significantly inhibited [3H]NE uptake by the cells in a concentration-dependent manner (1-100 microM). Kinetic analysis revealed that bisphenol A, as well as 17beta-estradiol, noncompetitively inhibited [3H]NE uptake. Bisphenol A and 17beta-estradiol inhibited the specific binding of [3H]desipramine to plasma membranes isolated from bovine adrenal medulla. As shown by Scatchard analysis of [3H]desipramine binding, bisphenol A increased the dissociation constant (K(d)) and decreased the maximal binding (B(max)), indicating a mixed type of inhibition. 17beta-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 17beta-estradiol in the adrenal medulla and probably in the brain noradrenergic neurons.
authors.affiliation: Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu 807-8555, Japan. toyohira@med.uoeh-u.ac.jp
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Toyohira
authors.forename: Kensuke
authors.initials: K
authors.lastname: Utsunomiya
authors.forename: Susumu
authors.initials: S
authors.lastname: Ueno
authors.forename: Kouichiro
authors.initials: K
authors.lastname: Minami
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Uezono
authors.forename: Reiji
authors.initials: R
authors.lastname: Yoshimura
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Futoshi
authors.initials: F
authors.lastname: Izumi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagihara
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001559:Benzhydryl Compounds; D001692:Biological Transport / Q000187:drug effects; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003891:Desipramine / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010636:Phenols / Q000494:pharmacology*; D027981:Symporters / Q000378:metabolism*; D014316:Tritium; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003891:Desipramine; D004958:Estradiol; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D009638:Norepinephrine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010636:Phenols; D027981:Symporters; D014316:Tritium; C006780:bisphenol A; D000098826:Bisphenol A Compounds