Recent advances in our understanding of 1,25-dihydroxyvitamin D(3) regulation of intestinal calcium absorption

Abstract

Calcium is required for many cellular processes including muscle contraction, nerve pulse transmission, stimulus secretion coupling and bone formation. The principal source of new calcium to meet these essential functions is from the diet. Intestinal absorption of calcium occurs by an active transcellular path and by a non-saturable paracellular path. The major factor influencing intestinal calcium absorption is vitamin D and more specifically the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). This article emphasizes studies that have provided new insight related to the mechanisms involved in the intestinal actions of 1,25(OH)(2)D(3). The following are discussed: recent studies, including those using knock out mice, that suggest that 1,25(OH)(2)D(3) mediated calcium absorption is more complex than the traditional transcellular model; evidence for 1,25(OH)(2)D(3) mediated active transport of calcium by distal as well as proximal segments of the intestine; 1,25(OH)(2)D(3) regulation of paracellular calcium transport and the role of 1,25(OH)(2)D(3) in protection against mucosal injury.

Figure 1

Time dependent effect of 1,25(OH)₂D₃ on duodenal absorption of ⁴⁷Ca in vitamin D deficient (top panel) and vitamin D replete (bottom panel) chicks. Chicks were injected (i.v.) with 1ug 1,25(OH)₂D₃ and duodenal calcium absorption was measured by the in situ ligated loop procedure. *Significant difference from zero time controls (p < 0.05). [from RH. Wasserman 2005 with permission; 3].

Figure 2

Model of vitamin D mediated intestinal calcium absorption. The traditional model of transcellular calcium transport consists of influx through an apical calcium channel (TRPV6), diffusion through the cytosol and active extrusion at the basolateral membrane by the plasma membrane ATPase (PMCA1b). Although entry of calcium has been reported to involve TRPV6, other calcium channels may also be involved. Calcium binding proteins including calmodulin and calbindin-D_9k (CaBP_9k) may be important for fine tuning calcium channel activity. In the cytosol calcium may be bound to calbindin as well as other calcium binding proteins. Calbindin as well as other calcium binding proteins may act to prevent toxic levels of calcium from accumulating in the cell. Calcium may also be sequestered by intracellular organelles ie. endoplasmic reticulum and mitochrondria which could also contribute to the protection of the cell against excessively high calcium. Increasing evidence supports regulation by 1,25(OH)₂D₃ of paracellular calcium transport.