Intestinal Na+/Ca2+ exchanger protein and gene expression are regulated by 1,25(OH)2D3 in vitamin D-deficient chicks

The role of 1,25(OH)2D3 on the intestinal NCX activity was studied in vitamin D-deficient chicks (-D) as well as the hormone effect on NCX1 protein and gene expression and the potential molecular mechanisms underlying the responses. Normal, -D and -D chicks treated with cholecalciferol or 1,25(OH)2D3 were employed. In some experiments, -D chicks were injected with cycloheximide or with cycloheximide and 1,25(OH)2D3 simultaneously. NCX activity was decreased by -D diet, returning to normal values after 50 IU daily of cholecalciferol/10 days or a dose of 1 μg calcitriol/kg of b.w. for 15 h. Cycloheximide blocked NCX activity enhancement produced by 1,25(OH)2D3. NCX1 protein and gene expression were diminished by -D diet and enhanced by 1,25(OH)2D3. Vitamin D receptor expression was decreased by -D diet, effect that disappeared after 1,25(OH)2D3 treatment. Rapid effects of 1,25(OH)2D3 on intestinal NCX activity were also demonstrated. The abolition of the rapid effects through addition of Rp-cAMPS and staurosporine suggests that non genomic effects of 1,25(OH)2D3 on NCX activity are mediated by activation of PKA and PKC pathways. In conclusion, 1,25(OH)2D3 enhances the intestinal NCX activity in -D chicks through genomic and non genomic mechanisms.