Intestinal calcium transport: pleiotropic effects mediated by vitamin D

The primary biological response to vitamin D is an increase in intestinal calcium transport. Efforts to elucidate the molecular mechanism by which this increased transport occurs has revealed that vitamin D mediates pleiotropic effects that are most likely a result of both genomic and nongenomic mechanisms of action of vitamin D. The spectrum of intestinal responses to vitamin D must now include an alteration in the topography of intestinal epithelial cells' brush border membrane (BBM). Initial indications of such an event were obtained with the polyene antibiotic filipin. Filipin induces active calcium transport in vitro in the small intestine of vitamin D-deficient chicks by specifically interacting with cholesterol and thereby altering membrane organization. Alterations in BBM topography in response to vitamin D were detected with the use of membrane-impermeable protein-labeling reagents and limited proteolysis. Administration of vitamin D to vitamin D-deficient chicks induces specific changes in accessibility of BBM proteins to labeling reagents. In addition, an alteration is induced in the rate of solubilization of BBM hydrolases during limited proteolysis. These vitamin D-mediated alterations in membrane topography offer new possibilities for regulation of intestinal calcium transport.