Cell-polarity dependent effect of chelation on the paracellular permeability of confluent caco-2 cell monolayers

Arthur B.J. Noach, Yuji Kurosaki, Margret C.M. Blom-Roosemalen, Albertus G. de Boer, Douwe D. Breimer

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

To investigate the effect of extracellular chelation at the apical, basolateral or both sides on the resistance and permeability of epithelial cell layers, we used 15 days cultures of a human intestinal adenocarcinoma cell line (Caco-2) and hydrophilic FITC-labeled dextran model compounds of various molecular weights. Transport of these hydrophilic compounds is restricted to the paracellular pathway in which the tight junctions form a barrier. Tight junctions are dependent on extracellular calcium and magnesium for their integrity and function. Calcium and magnesium chelation with 2.5 mM EDTA at the apical and basolateral side of the monolayer resulted in a drastic drop, up to 80% of the initial value, in trans-epithelial electrical resistance after 60 min. Application at the basolateral side resulted in a drop of 40% in resistance, while application on the apical side almost did not give any effect. The same pattern was also found in transepithelial clearance studies with fluorescein-Na and FITC-labeled dextran model compounds with molecular weights ranging from 4000 to 500 000. After 2.5 mM EDTA treatment on both sides a maximal (1400-fold) enhancement in transport clearance occurred for the dextran molecule with molecular weight 20 000 (Stokes-Einstein molecular radius 30 Å). For basolateral calcium and magnesium chelation similar results were found, however, with lesser maximal effects. For apical application no transport enhancement could be found with 2.5 mM EDTA. These results have shown that transport of hydrophilic compounds through epithelial monolayers is enhanced more effectively by basolateral application of EDTA than by apical application.

Original languageEnglish
Pages (from-to)229-237
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume90
Issue number3
DOIs
Publication statusPublished - Mar 31 1993
Externally publishedYes

Keywords

  • Absorption
  • Cell-polarity
  • EDTA, Caco-2 cell line
  • Enhancer
  • Tight junctions

ASJC Scopus subject areas

  • Pharmaceutical Science

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