Effects of selective estrogen receptor modulators on plasma membrane estrogen receptors and catecholamine synthesis and secretion in cultured bovine adrenal medullary cells

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 [3h]17b-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 mm,whereas tamoxifen (1.0 nm - 10 mm) increased binding at all concentrations (except for 100 nm). tamoxifen at 100 nm caused a significant increase in basal 14c-catecholamine synthesis from [ 14c]tyrosine,whereas tamoxifen and raloxifene at higher concentrations attenuated basal and acetylcholine-induced 14c- catecholamine synthesis. raloxifene (0.3,1.0,and 3 - 100 mm) and tamoxifen (10 - 100 mm) also suppressed catecholamine secretion and 45ca 2+ and 22na+ influx,respectively,induced by acetylcholine. raloxifene (1.0 mm) inhibited na+ current evoked by acetylcholine in xenopus oocytes expressing a4b2 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. © the japanese pharmacological society.