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Am J Physiol Gastrointest Liver Physiol 274: G389-G396, 1998;
0193-1857/98 $5.00
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Vol. 274, Issue 2, G389-G396, February 1998

Vitamin D increases tight-junction conductance and paracellular Ca2+ transport in Caco-2 cell cultures

Mary V. Chirayath, Leszek Gajdzik, Wolfgang Hulla, Jürg Graf, Heide S. Cross, and Meinrad Peterlik

Department of General and Experimental Pathology, University of Vienna, A-1090 Vienna, Austria

We investigated the effects of 1alpha ,25-dihydroxyvitamin D3 [1,25(OH)2D3] on paracellular intestinal Ca2+ absorption by determination of transepithelial electric resistance (TEER), as a measure of tight-junction ion permeability and bidirectional transepithelial 45Ca2+ fluxes in confluent Caco-2 cell cultures. The rise of TEER to steady-state levels of ~2,000 Omega  · cm2 was significantly attenuated by 1,25(OH)2D3 (by up to 50%) in a dose-dependent fashion between 10-11 and 10-8 M. Synthetic analogs of 1,25(OH)2D3, namely, 1alpha ,25-dihydroxy-16-ene,23-yne-vitamin D3 and 1alpha ,25-dihydroxy-26,27-hexafluoro-16-ene,23-yne-vitamin D3, exhibited similar biopotency, whereas their genomically inactive 1-deoxy congeners were only marginally effective. Enhancement of transepithelial conductance of Caco-2 cell monolayers by vitamin D was accompanied by a significant increase in bidirectional transepithelial 45Ca2+ fluxes. Although 1,25(OH)2D3 also induced cellular 45Ca2+ uptake from the apical aspect of Caco-2 cell layers and upregulated the expression of calbindin-9kDa mRNA, no significant contribution of the Ca2+-adenosinetriphosphatase-mediated transcellular pathway to transepithelial Ca2+ transport could be detected. Therefore stimulation of Ca2+ fluxes across confluent Caco-2 cells very likely results from a genomic effect of vitamin D sterols on assembly and permeability of tight-junctional complexes.

intestinal calcium absorption; 1alpha ,25-dihydroxyvitamin D3; synthetic vitamin D compounds; vitamin D receptor; genomic action; ionic conductance; cellular calcium uptake; calbindin-9kDa; calcium-adenosinetriphosphatase


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