Selective inhibition of L-type Ca2+ channels in A7r5 cells by physiological levels of testosterone

被引:83
作者
Hall, J.
Jones, R. D.
Jones, T. H.
Channer, K. S.
Peers, C. [1 ]
机构
[1] Univ Leeds, Sch Med, Leeds LS2 9JT, W Yorkshire, England
[2] Barnsly Hosp NHS Fdn Trust, Barnsley S75 2EP, England
[3] Univ Sheffield, Div Genom Med, Acad Unit Endocrinol, Hormone & Vasc Biol Res Ctr, Sheffield S10 2RX, S Yorkshire, England
[4] Royal Hallamshire Hosp, Dept Cardiol, Sheffield S10 2JF, S Yorkshire, England
关键词
D O I
10.1210/en.2005-1243
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Testosterone has marked beneficial cardiovascular effects, many of which have been attributed to a vasodilatory action. However, the molecular target of testosterone underlying this effect is subject to debate. In this study, we have used microfluorimetry as a noninvasive means of examining whether testosterone could exert dilatory effects via inhibition of voltage-gated Ca2+ entry in the model vascular smooth muscle cell line, A7r5. Rises of [Ca2+](i) evoked by 50 mM K+-containing solution were suppressed in a concentration-dependent manner by testosterone (IC50, 3.1 nM) and by the nonaromatizable analog, 5 beta-dihydrotestosterone (IC50, 6.9 nM). The effects of testosterone were apparent in the presence of pimozide (to block T-type Ca2+ channels) but not nifedipine (to block L-type Ca2+ channels). Testosterone did not alter Ca2+ mobilization from intracellular stores by the prostaglandin analog U46619 or capacitative Ca2+ entry in cells pretreated with thapsigargin. Our results indicate that testosterone, at physiological concentrations, can selectively suppress Ca2+ entry into A7r5 cells via L-type Ca2+ channels. We suggest this effect is a likely mechanism underlying its vasodilatory actions and beneficial cardiovascular effects.
引用
收藏
页码:2675 / 2680
页数:6
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