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 Ca2+ reabsorption. Therefore, here we investigated whether extracellular calcium (Ca(o)2+) can regulate active or passive 45Ca2+ 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 Ca2+ permeability but failed to alter active Ca2+ transport. The Ca(o)2+ effect on TER was rapid, sustained and concentration-dependent. Increasing basolateral Mg2+ concentration increased TER and inhibited both passive and active Ca2+ 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 Ca2+ 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 Ca2+ absorption.
Davies
Sarah L
SL
Faculty of Life Sciences, University of Manchester, Manchester, UK.
Gibbons
Claire E
CE
Steward
Martin C
MC
Ward
Donald T
DT
D000494:Allosteric Regulation; D001692:Biological Transport / Q000502:physiology; D018938:Caco-2 Cells / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002762:Cholecalciferol / Q000378:metabolism; D006801:Humans; D008274:Magnesium / Q000378:metabolism*; D044169:Receptors, Calcium-Sensing / Q000378:metabolism
D044169:Receptors, Calcium-Sensing; D002762:Cholecalciferol; D008274:Magnesium; D002118:Calcium