Rapid 1,25(OH)2-vitamin D3 stimulation of calcium uptake by rat intestinal cells involves a dihydropyridine-sensitive cAMP-dependent pathway.

The acute effects of 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) on Ca2+ influx in isolated rat enterocytes were studied. The hormone significantly increased 45Ca2+ uptake by the cells within 1-10 min in a specific dose-dependent manner (10(-11)-10(-9) M) since 25(OH)D3 and 24,25(OH)2D3 were devoid of activity. The effects of 1,25(OH)2D3 were mimicked by the Ca2+ channel agonist BAY K8644 and completely abolished by nifedipine (1 microM) and verapamil (10 microM). Incubation of duodenal cells with 1,25(OH)2D3 rapidly (1-5 min) increased cAMP levels. Forskolin caused a rapid increase in Ca2+ uptake by enterocytes which was similar to the action of the hormone. Moreover, pretreatment of cells with the specific cAMP inhibitor Rp-cAMPS suppressed the changes in 45Ca influx induced by 1,25(OH)2D3. These results provide the first evidence involving Ca2+ channel activation through the cAMP pathway by 1,25(OH)2D3 in mammalian intestinal cells.