NONNUCLEAR EFFECTS OF THE STEROID-HORMONE 1-ALPHA,25(OH)(2)-VITAMIN D-3 - ANALOGS ARE ABLE TO FUNCTIONALLY DIFFERENTIATE BETWEEN NUCLEAR AND MEMBRANE-RECEPTORS
NONNUCLEAR EFFECTS OF THE STEROID-HORMONE 1-ALPHA,25(OH)(2)-VITAMIN D-3 - ANALOGS ARE ABLE TO FUNCTIONALLY DIFFERENTIATE BETWEEN NUCLEAR AND MEMBRANE-RECEPTORS
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DOI：
10.1006/bbrc.1994.1714
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发表时间：
1994-05-30
影响因子：
3.1
通讯作者：
NORMAN, AW
中科院分区：
文献类型：
--
作者：
DORMANEN, MC;BISHOP, JE;NORMAN, AW
类固醇激素1 α，25-二羟基维生素D-3 [1 α，25(OH)(2)D-3]通过基因组机制和非基因组机制（打开电压门控制的Ca2+通道）刺激生物反应。我们在这里报道了两个封闭的b环类固醇类似物，1 α,25(OH)(2) d - 3,1 α,25(OH)(2)-7-脱氢胆固醇和1 α，25(OH)(2)-lumisterol(3)，能够产生非基因组反应，经scaltachia，而没有能力与天然代谢物竞争与其核受体的结合。我们认为非基因组膜相关受体可以接受封闭的6-s-顺式构象的配体，而核受体更喜欢扩展的6-s-反式构象。(C) 1994学术出版社，Inc.
The steroid hormone 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3] stimulates biological responses via both genomic mechanisms and nongenomic mechanisms (opening of voltage-gated Ca2+ channels). We report here that the two closed B-ring steroid analogs of 1 alpha,25(OH)(2)D-3, 1 alpha,25(OH)(2)-7-dehydrocholesterol and 1 alpha,25(OH)(2)-lumisterol(3), are able to generate the nongenomic response, transcaltachia, without the ability to compete with the natural metabolite for binding to its nuclear receptor. We propose that the nongenomic membrane associated receptor can accept the ligand in its closed ''6-s-cis'' conformation whereas the nuclear receptor prefers the extended ''6-s-trans'' conformer. (C) 1994 Academic Press, Inc.