Molecular aspects of intestinal calcium absorption
- PMID: 26109800
- PMCID: PMC4476875
- DOI: 10.3748/wjg.v21.i23.7142
Molecular aspects of intestinal calcium absorption
Abstract
Intestinal Ca(2+) absorption is a crucial physiological process for maintaining bone mineralization and Ca(2+) homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca(2+) across the brush border membranes (BBM) of enterocytes through epithelial Ca(2+) channels TRPV6, TRPV5, and Cav1.3; Ca(2+) movement from the BBM to the basolateral membranes by binding proteins with high Ca(2+) affinity (such as CB9k); and Ca(2+) extrusion into the blood. Plasma membrane Ca(2+) ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca(2+) 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 Ca(2+) 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 Ca(2+) transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca(2+) absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca(2+) transport to control values. Calcitriol [1,25(OH)₂D₃] is the major controlling hormone of intestinal Ca(2+) 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 Ca(2+) 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 Ca(2+) absorption according to Ca(2+) demands. Better knowledge of the molecular details of intestinal Ca(2+) absorption could lead to the development of nutritional and medical strategies for optimizing the efficiency of intestinal Ca(2+) absorption and preventing osteoporosis and other pathologies related to Ca(2+) metabolism.
Keywords: 1,25(OH)2D3; Aging; Estrogen; Intestinal Ca2+ absorption; Lactation; PTH; Paracellular route; Pregnancy; Prolactin; Transcellular pathway.
Figures
![Figure 1](http://178.128.105.246/cars-https-www.ncbi.nlm.nih.gov/pmc/articles/instance/4476875/bin/WJG-21-7142-g001.gif)
![Figure 2](http://178.128.105.246/cars-https-www.ncbi.nlm.nih.gov/pmc/articles/instance/4476875/bin/WJG-21-7142-g002.gif)
Similar articles
-
Expression of transcellular and paracellular calcium and magnesium transport proteins in renal and intestinal epithelia during lactation.Am J Physiol Renal Physiol. 2017 Sep 1;313(3):F629-F640. doi: 10.1152/ajprenal.00680.2016. Epub 2017 May 24. Am J Physiol Renal Physiol. 2017. PMID: 28539338
-
Dietary and pharmacological compounds altering intestinal calcium absorption in humans and animals.Nutr Res Rev. 2015 Dec;28(2):83-99. doi: 10.1017/S0954422415000050. Epub 2015 Oct 15. Nutr Res Rev. 2015. PMID: 26466525
-
Fibroblast growth factor-23 negates 1,25(OH)2D3-induced intestinal calcium transport by reducing the transcellular and paracellular calcium fluxes.Arch Biochem Biophys. 2013 Aug 1;536(1):46-52. doi: 10.1016/j.abb.2013.05.009. Epub 2013 Jun 4. Arch Biochem Biophys. 2013. PMID: 23747333
-
Minireview on regulation of intestinal calcium absorption. Emphasis on molecular mechanisms of transcellular pathway.Digestion. 2008;77(1):22-34. doi: 10.1159/000116623. Epub 2008 Feb 15. Digestion. 2008. PMID: 18277073 Review.
-
[Intestinal absorption of calcium and its regulation. Tissue, membrane and molecular events].Diabete Metab. 1984 May;10(2):106-20. Diabete Metab. 1984. PMID: 6378683 Review. French.
Cited by
-
The Effects of Acid on Calcium and Phosphate Metabolism.Int J Mol Sci. 2024 Feb 8;25(4):2081. doi: 10.3390/ijms25042081. Int J Mol Sci. 2024. PMID: 38396761 Free PMC article. Review.
-
PMAIP1, a novel diagnostic and potential therapeutic biomarker in osteoporosis.Aging (Albany NY). 2024 Feb 16;16(4):3694-3715. doi: 10.18632/aging.205553. Epub 2024 Feb 16. Aging (Albany NY). 2024. PMID: 38372699 Free PMC article.
-
Fermented foods and gastrointestinal health: underlying mechanisms.Nat Rev Gastroenterol Hepatol. 2024 Apr;21(4):248-266. doi: 10.1038/s41575-023-00869-x. Epub 2023 Dec 11. Nat Rev Gastroenterol Hepatol. 2024. PMID: 38081933 Review.
-
Ion channels and transporters regulate nutrient absorption in health and disease.J Cell Mol Med. 2023 Sep;27(18):2631-2642. doi: 10.1111/jcmm.17853. Epub 2023 Aug 28. J Cell Mol Med. 2023. PMID: 37638698 Free PMC article. Review.
-
Expert consensus on multidisciplinary approach to the diagnosis and treatment of primary hyperparathyroidism in pregnancy in China.Endocrine. 2023 Nov;82(2):282-295. doi: 10.1007/s12020-023-03392-w. Epub 2023 May 23. Endocrine. 2023. PMID: 37221429
References
-
- Alexander RT, Rievaj J, Dimke H. Paracellular calcium transport across renal and intestinal epithelia. Biochem Cell Biol. 2014;92:467–480. - PubMed
-
- Mori M, Tanifuji S, Mochida S. Kinetic organization of Ca2+ signals that regulate synaptic release efficacy in sympathetic neurons. Mol Pharmacol. 2014;86:297–305. - PubMed
-
- Bartlett PJ, Gaspers LD, Pierobon N, Thomas AP. Calcium-dependent regulation of glucose homeostasis in the liver. Cell Calcium. 2014;55:306–316. - PubMed
-
- Pérez AV, Picotto G, Carpentieri AR, Rivoira MA, Peralta López ME, Tolosa de Talamoni NG. Minireview on regulation of intestinal calcium absorption. Emphasis on molecular mechanisms of transcellular pathway. Digestion. 2008;77:22–34. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous