Brush-border membrane calcitriol

Induction of Calbindin-D In response to calcitriol administration, there is an increase in mRNA synthesis and then in the synthesis of calbindin-D in intestinal mucosal cells, which is correlated with the later and more sustained increase in calcium absorption. In vitamin D-deficient animals, there is no detectable calbindin in the intestinal mucosa, whereas in animals adequately provided with vitamin D, it may account for 1 % to 3% of soluble protein in the cytosol of the colunmar epithelial ceils. Although the rapid response to calcitriol is an increase in the permeability of the brush border membrane to calcium, the induction of calbindin permits intracellular accumulation and transport of calcium. The rapid increase in net calcium transport in tissue from vitamin D-replete animals is presumably dependent on the calbindin that is already present in deficient animals, there can be no increase in calcium transport until sufficient calbindin has accumulated to permit intracellular accumulation, despite the increased permeability of the brush border. 

Plausible as the above mechanism may seem, it may, however, not be the whole truth. An alternative mechanism is vesicular transport. In chicken intestine it has been shown that the only epithelial organelles that increased in Ca content as a result of calcitriol treatment were the lysosomes." The result lends support to a transport mechanism involving Ca + uptake across the brush-border membrane by endocytic vesicles, fusion of these vesicles with lysosomes, and possibly also delivery of Ca to the basal lateral membrane of the epithelial cell by exocytosis. This process would also explain the vitamin-D-induced alterations in brush-border-membrane lipid compositions as a consequences of preferential incorporation of certain types of lipids into the vesicles. Interestingly, the lysosomes in the chicken studies also contained high levels of calbin-... 

The mechanism of action of the vitamin D metabolites remains under active investigation. However, calcitriol is well established as the most potent agent with respect to stimulation of intestinal calcium and phosphate transport and bone resorption. Calcitriol appears to act on the intestine both by induction of new protein synthesis (eg, calcium-binding protein and TRPV6, an intestinal calcium channel) and by modulation of calcium flux across the brush border and basolateral membranes by a means that does not require new protein synthesis. The molecular action of calcitriol on bone has received less attention. However, like PTH, calcitriol can induce RANK ligand in osteoblasts and proteins such as osteocalcin, which may regulate the mineralization process. The metabolites 25(OH)D and 24,25(OH)2D are far less... 

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