Modulation by estrogens and xenoestrogens of recombinant human neuronal nicotinic receptors.
The effects of estrogens and xenoestrogens on human neuronal nicotinic acetylcholine receptor/channels were examined by expressing recombinant channels in Xenopus oocytes. When functional channels were expressed with alpha3 and beta4 subunits, estrogens (17beta-estradiol, 17alpha-estradiol, 17alpha-ethynylestradiol and diethylstilbestrol) and xenoestrogens (bisphenol A, p-nonylphenol and p-octylphenol) inhibited an ionic current activated by acetylcholine at concentrations up to 100 microM. When the subunit combination was changed to alpha4beta2, diethystilbestrol and the xenoestrogens inhibited the acetylcholine-activated current, but 17beta-estradiol or 17alpha-estradiol did not. For 17alpha-ethynylestradiol, the current through the alpha4beta2 receptor/channel was inhibited at 1 microM, but it was markedly enhanced at 10 and 100 microM. Tamoxifen (10 microM), an antiestrogen, itself inhibited the acetylcholine-activated current but did not antagonize the current modulations induced by the estrogens and the xenoestrogens. These and additional results suggest that human neuronal nicotinic acetylcholine receptors are the targets of non-genomic actions of estrogens and xenoestrogens.
Nakazawa
K
K
Division of Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, 158-8501, Tokyo, Japan. nakazawa@nihs.go.jp
Ohno
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001559:Benzhydryl Compounds; D004054:Diethylstilbestrol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes; D010636:Phenols / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology; D015262:Xenobiotics / Q000494:pharmacology*; D014981:Xenopus; D000098826:Bisphenol A Compounds
D000109:Acetylcholine; D001559:Benzhydryl Compounds; D004054:Diethylstilbestrol; D004958:Estradiol; D004967:Estrogens; D004997:Ethinyl Estradiol; D010636:Phenols; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D013629:Tamoxifen; D015262:Xenobiotics; C403530:nicotinic receptor alpha3beta4; C403531:nicotinic receptor alpha4beta2; C025256:nonylphenol; C080417:4-octylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds