Wilhelm F, Dauben W G, Kohler B, Roesle A, Norman A W
Arch Biochem Biophys. 1984 Aug 15;233(1):127-32. doi: 10.1016/0003-9861(84)90608-8.
The biological activity and the binding affinity for the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] intestinal receptor of a new fluorine-containing vitamin D compound, namely 6-fluoro-vitamin D3 (6-F-D3), is reported. A significant interaction of 6-F-D3 with the 1,25(OH)2D3 receptor was found, with a relative competitive index (RCI) of 0.26 +/- 0.04, which is intermediate between 25-hydroxyvitamin D3 (0.14 +/- 0.01) and 1 alpha-hydroxyvitamin D3 (0.46 +/- 0.08), where the RCI of 1,25(OH)2D3 is defined to be 100. In contrast, vitamin D3 was unable to interact with the 1,25(OH)2D3 receptor. Also, the biological activity of 6-F-D3 was assessed in vivo in the vitamin D-deficient chick. 6-F-D3 at doses up to 130 nmol displayed no biological action on either intestinal calcium absorption (ICA) or bone calcium mobilization (BCM) over the time interval of 14-48 h after dosing. However, when 130 nmol 6-F-D3 was given 2 h before and 6 h after vitamin D3 (1.62 nmol), a significant inhibition of vitamin D-mediated ICA was noted. Also, a dose of 130 nmol 6-F-D3 given 2 h before and 6 h after 1,25(OH)2D3 (0.26 nmol) significantly inhibited ICA, as measured at 12 h. 6-F-D3 is the first vitamin D analog found which has an ability to both bind to the 1,25(OH)2D3 receptor and to antagonize the production of biological responses by 1,25(OH)2D3.
报道了一种新型含氟维生素D化合物，即6-氟维生素D3（6-F-D3）对1,25-二羟基维生素D3[1,25(OH)2D3]肠道受体的生物活性和结合亲和力。发现6-F-D3与1,25(OH)2D3受体有显著相互作用，相对竞争指数（RCI）为0.26±0.04，介于25-羟基维生素D3（0.14±0.01）和1α-羟基维生素D3（0.46±0.08）之间，其中1,25(OH)2D3的RCI定义为100。相比之下，维生素D3不能与1,25(OH)2D3受体相互作用。此外，在维生素D缺乏的雏鸡体内评估了6-F-D3的生物活性。给药后14至48小时的时间间隔内，剂量高达130 nmol的6-F-D3对肠道钙吸收（ICA）或骨钙动员（BCM）均无生物学作用。然而，当在维生素D3（1.62 nmol）给药前2小时和给药后6小时给予130 nmol 6-F-D3时，观察到对维生素D介导的ICA有显著抑制作用。同样，在1,25(OH)2D3（0.26 nmol）给药前2小时和给药后6小时给予130 nmol 6-F-D3，在12小时测量时显著抑制了ICA。6-F-D3是首个被发现既能与1,25(OH)2D3受体结合又能拮抗1,25(OH)2D3产生生物反应的维生素D类似物。
