Intestinal Na +/Ca 2+ exchanger protein and gene expression are regulated by 1,25(OH) 2D 3 in vitamin D-deficient chicks

Abstract

The role of 1,25(OH) 2D 3 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) 2D 3 were employed. In some experiments, -D chicks were injected with cycloheximide or with cycloheximide and 1,25(OH) 2D 3 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) 2D 3. NCX1 protein and gene expression were diminished by -D diet and enhanced by 1,25(OH) 2D 3. Vitamin D receptor expression was decreased by -D diet, effect that disappeared after 1,25(OH) 2D 3 treatment. Rapid effects of 1,25(OH) 2D 3 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) 2D 3 on NCX activity are mediated by activation of PKA and PKC pathways. In conclusion, 1,25(OH) 2D 3 enhances the intestinal NCX activity in -D chicks through genomic and non genomic mechanisms.