Molecular events involved in 1,25-dihydroxyvitamin D3 stimulation of intestinal calcium transport.

There is a biphasic response of intestinal calcium transport to 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3). The first or rapid response is by existng mature villus cells, whereas the slow second response is by maturing crypt cells. For both responses, [3H]1,25-(OH)2-D3 localizes in the nucleus before initiating the transport events. This localization is brought about by a specific cytoplasmic receptor, which has a molecular weight of 67,000, is highly specific for 1,25-(OH)2-D3, and has a Kd of 5 X 10(-11) M. Its essentiality for intestinal calcium transport response to 1,25-(OH)2-D3 can be demonstrated in neonatal rat pups. In cultured chick intestinal duodena calcium transport begins to appear within 4 h after the addition of 1,25-(OH)2-D3. The response of this calcium transport system to 1,25-(OH)2-D3 is totally blocked by cycloheximide in a reversible manner. Similarly, it is blocked by actinomycin D in a partially reversible manner. These results make it obvious that the rapid calcium transport response to 1,25-(OH)2-D3 involves nuclear activity and transcription of DNA into functional proteins. The exact nature of the transport proteins remains largely unknown except for the calcium-binding protein originally discovered by Wasserman and colleagues. The transport proteins are believed to operate at the brush border membrane surface to facilitate the transfer of calcium and phosphorus into the absorption cells.