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  • Title: Stimulation by 1alpha,25(OH)2-vitamin D3 of whole cell chloride currents in osteoblastic ROS 17/2.8 cells. A structure-function study.
    Author: Zanello LP, Norman AW.
    Journal: J Biol Chem; 1997 Sep 05; 272(36):22617-22. PubMed ID: 9278418.
    Abstract:
    1alpha,25-Dihydroxyvitamin D3 (1alpha,25(OH)2D3) can generate biological responses via genomic and nongenomic mechanisms. This article reports for the first time the effects of 1alpha,25(OH)2D3 and structurally related analogs on whole cell chloride currents in osteoblastic cells. 1alpha,25(OH)2D3 promoted the rapid enhancement of outwardly rectifying Cl- currents in 93% of the osteoblasts in a concentration-dependent manner, with a maximal increase of about 4-fold between 0.5 and 5 nM. This effect of 1alpha,25(OH)2D3 was blocked by 1 nM stereoisomer 1beta,25(OH)2D3 when added to the bath before 1alpha,25(OH)2D3. On the other hand, 1 nM of the 6-s-cis locked analog 1alpha,25(OH)2-lumisterol3 significantly increased by about 2.2-fold outward Cl- currents in the ROS 17/2.8 cells, whereas the increase promoted by same concentration of the 6-s-trans locked analog 1alpha,25(OH)2-tachysterol (0.8-fold) was significantly lower, suggesting that the 6-s-cis locked or steroid-like form was preferred over the extended 6-s-trans conformer to promote these rapid effects of the hormone. We conclude that the agonist effects of 1alpha,25(OH)2D3 in osteoblasts at the cellular membrane level seem to be determined by some structural features of the molecule which may be crucial for its interaction with a putative membrane receptor in the cell surface.
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