Mechanism of action of 1,25-dihydroxyvitamin D3 on intestinal calcium absorption

Abstract

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is the major controlling hormone of intestinal calcium absorption. As the body's demand for calcium increases from a diet deficient in calcium, from growth, pregnancy or lactation, the synthesis of 1,25(OH)(2)D(3) is increased resulting in the stimulation of intestinal calcium absorption. However a complete description of the molecular mechanisms involved in the 1,25(OH)(2)D(3) regulated calcium absorptive process remains incomplete. Intestinal calcium absorption occurs by both an active saturable transcellular pathway and a passive nonsaturable paracellular pathway. Each step in the process of transcellular calcium transport (apical entry of calcium, translocation of calcium through the interior of the enterocyte and basolateral extrusion of calcium by the plasma membrane pump) has been reported to involve a vitamin D dependent component. This article will review recent studies, including those using knockout mice, that have suggested that 1,25(OH)(2)D(3) mediated calcium absorption is more complex than the traditional three step model of transcellular calcium transport. Current concepts are reviewed and questions that remain are addressed. Evidence for a role of 1,25(OH)(2)D(3) in the regulation of the paracellular pathway is also discussed.

Investigation of the effects of vitamin D and calcium on intestinal motility: In vitro tests and implications for clinical treatment

“…Calbindin D is a low molecular mass protein; increased synthesis of calbindin D results in extended absorption of calcium. The calbindin calcium binding domain is similar to that of calmodulin (12).…”

“…1a,25(OH) 2 D 3 stimulates calcium absorption, increasing permeability at the intestinal level and active transport. In addition, 1a,25(OH) 2 D 3 modifi es the binding between calmodulin and myosin I, a protein found in the intestinal villous (12). The binding of calmodulin to myosin promotes calcium entrance into the intestinal cells, while transport within the cytoplasm is ensured by calbindin D, whose synthesis is stimulated by calcitriol itself.…”

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

“…The two main routes of calcium absorption are an active, saturable, transcellular pathway that is stimulated by calcitriol and a passive, nonsaturable, paracellular pathway that is also stimulated in part by calcitriol (181,247). Rapid and active calcium absorption is thought to represent ϳ20% of net absorption, and it takes place largely in the duodenum of the rodent, while ϳ80% of calcium absorption occurs through slower, passive mechanisms in the jejunum and ileum, with lesser amounts in the colon (181,694).…”

“…Rapid and active calcium absorption is thought to represent ϳ20% of net absorption, and it takes place largely in the duodenum of the rodent, while ϳ80% of calcium absorption occurs through slower, passive mechanisms in the jejunum and ileum, with lesser amounts in the colon (181,694). Active intestinal calcium absorption is more important when dietary intake of calcium is limited.…”

“…Each of these factors is dependent on calcitriol for normal expression in nonpregnant animals (127,181,182,596,854). Each is upregulated in the intestines of pregnant mice and rats, and reaches the highest levels of expression by mid to late pregnancy (126,237,949,1021).…”