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 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.
Toyohira
Yumiko
Y
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
Utsunomiya
Kensuke
K
Ueno
Susumu
S
Minami
Kouichiro
K
Uezono
Yasuhito
Y
Yoshimura
Reiji
R
Tsutsui
Masato
M
Izumi
Futoshi
F
Yanagihara
Nobuyuki
N
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
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