Molecular aspects of intestinal calcium absorption

Abstract

Intestinal Ca²⁺ absorption is a crucial physiological process for maintaining bone mineralization and Ca²⁺ homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca²⁺ across the brush border membranes (BBM) of enterocytes through epithelial Ca²⁺ channels TRPV6, TRPV5, and Ca_v1.3; Ca²⁺ movement from the BBM to the basolateral membranes by binding proteins with high Ca²⁺ affinity (such as CB_9k); and Ca²⁺ extrusion into the blood. Plasma membrane Ca²⁺ ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca²⁺ from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca²⁺ transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca²⁺ transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca²⁺ absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca²⁺ transport to control values. Calcitriol [1,25(OH)₂D₃] is the major controlling hormone of intestinal Ca²⁺ transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca²⁺ transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)₂D₃ production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca²⁺ absorption according to Ca²⁺ demands. Better knowledge of the molecular details of intestinal Ca²⁺ absorption could lead to the development of nutritional and medical strategies for optimizing the efficiency of intestinal Ca²⁺ absorption and preventing osteoporosis and other pathologies related to Ca²⁺ metabolism.

Keywords: Intestinal Ca²⁺ absorption; Transcellular pathway; Paracellular route; 1,25(OH)₂D₃; PTH; Prolactin; Estrogen; Lactation; Pregnancy; Aging

Core tip: Intestinal Ca²⁺ absorption occurs through transcellular and paracellular pathways. Apparently, novel proteins, such as Ca_v1.3 and 4.1R, are involved in the Ca²⁺ transcellular pathway. Proteins involved in tight junction structures, such as claudins 2, 12, and 15, participate in the paracellular pathway. There is evidence of crosstalk between the transcellular and paracellular pathways. Better knowledge of the molecular details of intestinal Ca²⁺ absorption could lead to the development of nutritional and medical strategies for optimizing the efficiency of intestinal Ca²⁺ absorption and preventing osteoporosis and other pathologies related to Ca²⁺ metabolism.