Effects of Selective Estrogen Receptor Modulators on Plasma Membrane Estrogen Receptors and Catecholamine Synthesis and Secretion in Cultured Bovine Adrenal Medullary Cells

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Author(s)

    • Inagaki Hirohide Inagaki Hirohide
    • Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan|Department of Obstetrics and Gynecology, School of Medicine, University of Occupational and Environmental Health, Japan
    • Ueno Susumu
    • Department of Occupational Toxicology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan
    • Obara Go
    • Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, Japan
    • Kawagoe Toshinori
    • Department of Obstetrics and Gynecology, School of Medicine, University of Occupational and Environmental Health, Japan
    • Tsutsui Masato
    • Department of Pharmacology, Graduate School of Medicine, University of The Ryukyus, Japan
    • Hachisuga Toru
    • Department of Obstetrics and Gynecology, School of Medicine, University of Occupational and Environmental Health, Japan
    • Yanagihara Nobuyuki
    • Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan

Abstract

We previously reported the occurrence and function of plasma membrane estrogen receptors in cultured bovine adrenal medullary cells. Here we report the effects of raloxifene and tamoxifen, selective estrogen receptor modulators, on plasma membrane estrogen receptors and catecholamine synthesis and secretion in these cells. Raloxifene caused dual effects on the specific binding of [<sup>3</sup>H]17<i>β</i>-estradiol to the plasma membranes isolated from bovine adrenal medulla; that is, it had a stimulatory effect at 1.0 – 10 nM but an inhibitory effect at 1.0 – 10 <i>μ</i>M, whereas tamoxifen (1.0 nM – 10 <i>μ</i>M) increased binding at all concentrations (except for 100 nM). Tamoxifen at 100 nM caused a significant increase in basal <sup>14</sup>C-catecholamine synthesis from [<sup>14</sup>C]tyrosine, whereas tamoxifen and raloxifene at higher concentrations attenuated basal and acetylcholine-induced <sup>14</sup>C-catecholamine synthesis. Raloxifene (0.3, 1.0, and 3 – 100 <i>μ</i>M) and tamoxifen (10 – 100 <i>μ</i>M) also suppressed catecholamine secretion and <sup>45</sup>Ca<sup>2+</sup> and <sup>22</sup>Na<sup>+</sup> influx, respectively, induced by acetylcholine. Raloxifene (1.0 <i>μ</i>M) inhibited Na<sup>+</sup> current evoked by acetylcholine in <i>Xenopus</i> oocytes expressing <i>α</i>4<i>β</i>2 neuronal nicotinic acetylcholine receptors. The present findings suggest that raloxifene and tamoxifen at low concentrations allosterically modulate plasma membrane estrogen receptors and at high concentrations inhibit acetylcholine-induced catecholamine synthesis and secretion by inhibiting Na<sup>+</sup> and Ca<sup>2+</sup> influx in bovine adrenal medulla.

Journal

  • Journal of Pharmacological Sciences

    Journal of Pharmacological Sciences 124(1), 66-75, 2014

    The Japanese Pharmacological Society

Codes

  • NII Article ID (NAID)
    130003382627
  • NII NACSIS-CAT ID (NCID)
    AA11806667
  • Text Lang
    ENG
  • ISSN
    1347-8613
  • NDL Article ID
    025159453
  • NDL Call No.
    Z53-D199
  • Data Source
    NDL  J-STAGE 
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