1α, 25-Dihydroxyvitamin D
3 [1α, 25(OH)
2D
3] has been shown to exert both is nuclear vitamin D receptor (nVDR)-mediated genomic actions and membrane vitamin D receptor (mVDR)-mediated nongenomic actions. In this study, the effects of 1α, 25(OH)
2D
3 and its analogues on transmembrane Ca
2+ influx were examined in the growth phase of rat osteosarcoma ROS17/2.8 cells. Like BAYK8644 (2×10
-5 M), a well-known L-type Ca
2+ channel agonist, 1α, 25(OH)
2D
3 (10
-8 M) increased transmembrane influx of Ca
2+ through voltage-dependent Ca
2+ channels and increased intracellular Ca
2+ concentration within 2 min of addition to the medium. The 1α, 25(OH)
2D
3-induced Ca
2+ influx was completely blocked by pre-treatment with nifedipine (2×10
-5 M), an L-type Ca
2+ channel antagonist. Two vitamin D analogues, 22-oxa-1α, 25(OH)
2D
3 (OCT, 10
-8 M) and 20-epi-22-oxa-24a, 26a, 27a-trihomo-1α, 25(OH)
2D
3 (KH1060, 10
-8 M), which were 3.8 and 3600-fold more active than 1α, 25(OH)
2D
3 in stimulating differentiation on human promyelocytic leukemic HL-60 cells, respectively, also increased intracellular Ca
2+ concentration, while their Ca
2+ channeling activities were similar to or significantly weaker than that of 1α, 25(OH)
2D
3. Furthermore, the enhanced transmembrane Ca
2+ influx induced by 1α, 25(OH)
2D
3 (10
-8 M) or OCT (10
-8 M) was completely blocked by pre-treatment with the respective 1β epimer [1β, 25(OH)
2D
3 and 1β-OCT] at equal concentration. These findings suggest that 1α, 25(OH)
2D
3 and its analogues modulate transmembrane Ca
2+ influx in osteoblast-like cells by opening L-type Ca
2+ channels which can recognize 1α-hydroxy analogues as agonists and 1β-hydroxy analogues as antagonists.
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