RECEPTOR-MEDIATED RAPID ACTION OF 1-ALPHA,25-DIHYDROXYCHOLECALCIFEROL - INCREASE OF INTRACELLULAR CGMP IN HUMAN-SKIN FIBROBLASTS
RECEPTOR-MEDIATED RAPID ACTION OF 1-ALPHA,25-DIHYDROXYCHOLECALCIFEROL - INCREASE OF INTRACELLULAR CGMP IN HUMAN-SKIN FIBROBLASTS
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DOI：
10.1073/pnas.85.4.1223
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发表时间：
1988-02-01
影响因子：
11.1
通讯作者：
MARX, SJ
中科院分区：
文献类型：
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作者：
BARSONY, J;MARX, SJ
正常人培养成纤维细胞胞内cGMP浓度增加1 - 2倍至3倍。, 25-dihydroxycholecalciferol [1. alpha。， 25-(OH)2D3]在0.01 nM ~ 1 μ m范围内呈剂量依赖性。反应可在1分钟内检测到，最高可达225%。在6-8分钟时为基线的8%)，在30分钟时不再检测到。α的半最大值效应。，25-(OH)2D3为1.8 nMI, 24,25-二羟基胆骨化醇的EC50估计高出100倍。1. beta。25-二羟基胆骨化醇、25-羟基胆骨化醇和胆骨化醇没有可检测到的影响。人类皮肤成纤维细胞有三种不同类型的1。，25-(OH)2D3受体缺陷对1. α无反应。，25-(OH)2，D3暴露随cGMP增加；然而，同样的细胞（像正常细胞一样）对睾酮或硝普钠有反应，cGMP迅速上升。我们得出结论，cGMP对钙化醇的反应迅速上升，显示了1. α的EC50。，25-(OH)2D3，胆钙化醇类似物特异性，以及细胞系依赖性，这些都表明通过特异性1. α介导。, 25 (OH) 2 d3受体。
The intracellular cGMP concentration in normal human cultured fibroblasts was increased 2- to 3-fold by 1.alpha.,25-dihydroxycholecalciferol [1.alpha., 25-(OH)2D3] in a dose-dependent manner between 0.01 nM and 1 .mu.M. The response was detectable within 1 min, reached a maximum (225% .+-. 8% of baseline) at 6-8 min, and was no longer detectable at 30 min. The half-maximal effect of 1.alpha.,25-(OH)2D3 was at 1.8 nMI, and 24,25-dihydroxycholecalciferol showed an estimated EC50 100-fold higher. 1.beta.,25-Dihydroxycholecalciferol, 25-hydroxycholecalciferol, and cholecalciferol had no detectable effect. Human skin fibroblasts with three different types of 1.alpha.,25-(OH)2D3 receptor defect did not respond to 1.alpha.,25-(OH)2,D3 exposure with cGMP increase; however, the same cells (like normal cells) responded to testosterone or sodium nitroprusside with a rapid rise of cGMP. We conclude that the rapid rise of cGMP in response to calciferols shows an EC50 for 1.alpha.,25-(OH)2D3, a cholecalciferol analog specificity, and a cell line dependency that are all suggestive of mediation through a specific 1.alpha.,25-(OH)2D3 receptor.