title: Effects of selective estrogen receptor modulators on plasma membrane estrogen receptors and catecholamine synthesis and secretion in cultured bovine adrenal medullary cells.
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 [(3)H]17β-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 μM, whereas tamoxifen (1.0 nM - 10 μM) increased binding at all concentrations (except for 100 nM). Tamoxifen at 100 nM caused a significant increase in basal (14)C-catecholamine synthesis from [(14)C]tyrosine, whereas tamoxifen and raloxifene at higher concentrations attenuated basal and acetylcholine-induced (14)C-catecholamine synthesis. Raloxifene (0.3, 1.0, and 3 - 100 μM) and tamoxifen (10 - 100 μM) also suppressed catecholamine secretion and (45)Ca(2+) and (22)Na(+) influx, respectively, induced by acetylcholine. Raloxifene (1.0 μM) inhibited Na(+) current evoked by acetylcholine in Xenopus oocytes expressing α4β2 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(+) and Ca(2+) influx in bovine adrenal medulla.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Japan.
authors.forename: Hirohide
authors.initials: H
authors.lastname: Inagaki
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Toyohira
authors.forename: Keita
authors.initials: K
authors.lastname: Takahashi
authors.forename: Susumu
authors.initials: S
authors.lastname: Ueno
authors.forename: Go
authors.initials: G
authors.lastname: Obara
authors.forename: Toshinori
authors.initials: T
authors.lastname: Kawagoe
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Toru
authors.initials: T
authors.lastname: Hachisuga
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagihara
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000096:biosynthesis* / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D009865:Oocytes / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D012964:Sodium; D013629:Tamoxifen / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism; D014981:Xenopus
chemical_list: D002395:Catecholamines; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D014443:Tyrosine; D020849:Raloxifene Hydrochloride; D012964:Sodium; D000109:Acetylcholine; D002118:Calcium