Extracellular calcium- and magnesium-mediated regulation of passive calcium transport across Caco-2 monolayers

The calcium-sensing receptor (CaR) is expressed on intestinal epithelial serosal membrane and in Caco-2 cells. In renal epithelium, CaR expressed on the basolateral membrane acts to limit excess tubular Ca 2+ reabsorption. Therefore, here we investigated whether extracellular calcium (Ca o 2+) can r...

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Published in:Biochimica et biophysica acta 2008-10, Vol.1778 (10), p.2318-2324
Main Authors: Davies, Sarah L., Gibbons, Claire E., Steward, Martin C., Ward, Donald T.
Format: Article
Language:English
Subjects:
Allosteric Regulation
Biological Transport - physiology
Caco-2 Cells - cytology
Caco-2 Cells - metabolism
Calcium
Calcium - metabolism
Cholecalciferol - metabolism
Epithelial transport
Humans
Intestine
Magnesium
Magnesium - metabolism
Receptors, Calcium-Sensing - metabolism
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Summary:The calcium-sensing receptor (CaR) is expressed on intestinal epithelial serosal membrane and in Caco-2 cells. In renal epithelium, CaR expressed on the basolateral membrane acts to limit excess tubular Ca 2+ reabsorption. Therefore, here we investigated whether extracellular calcium (Ca o 2+) can regulate active or passive 45Ca 2+ transport across differentiated Caco-2 monolayers via CaR-dependent or CaR-independent mechanisms. Raising the Ca o 2+ concentration from 0.8 to 1.6 mM increased transepithelial electrical resistance (TER) and decreased passive Ca 2+ permeability but failed to alter active Ca 2+ transport. The Ca o 2+ effect on TER was rapid, sustained and concentration-dependent. Increasing basolateral Mg 2+ concentration increased TER and inhibited both passive and active Ca 2+ transport, whereas spermine and the CaR-selective calcimimetic NPS R-467 were without effect. We conclude that small increases in divalent cation concentration elicit CaR-independent increases in TER and inhibit passive Ca 2+ transport across Caco-2 monolayers, most probably through a direct effect on tight junction permeability. Whilst it is known that the complete removal of Ca o 2+ lowers TER, here we show that Ca o 2+ addition actually increases TER in a concentration-dependent manner. Therefore, such Ca o 2+-sensitivity could modulate intestinal solute transport including the limiting of excess Ca 2+ absorption.
ISSN:0005-2736
0006-3002
1879-2642
DOI:10.1016/j.bbamem.2008.05.013