Effects of anti-oestrogens and beta-estradiol on calcium uptake by cardiacsarcoplasmic reticulum

1 Tamoxifen and a group of structurally similar non-steroidal, triphenolic compounds inhibit the oestrogen receptor. In addition to this action, these anti-oestrogens are known to inhibit some types of plasma membrane ion cha nnels and other proteins through mechanisms that do not appear to involve t heir interactions with the estrogen receptor but could be the result of the ir effect on membrane lipid structure or fluidity. 2 We studied the effects of beta -estradiol and three anti-oestrogens (tamo xifen, 4-hydroxytamoxifen and clomiphene) on Ca2+ uptake into sarcoplasmic reticulum (SR) vesicles isolated from canine cardiac ventricular tissue. 3 The antiestrogens all inhibit SR Ca2+ uptake in a concentration-dependent manner (order of potency: tamoxifen > 4-hydroxytamoxifen greater than or e qual to clomiphene). Although these compounds rapidly inhibit net Ca2+ upta ke they do not have a similar rapid effect on the ATPase activity of the SR Ca pump. beta -estradiol has no effect on Ca2+ uptake nor does it alter th e inhibitory action of tamoxifen on the SR. 4 The differences in the effects of beta -estradiol and the anti-oestrogens on cardiac SR Ca2+ uptake do not correlate with differences in the ways in which these compounds have been reported to interact with membrane lipids. Our results are consistent, however, with direct effects on a membrane pro tein (possibly an SR Cl- or K+ channel).