Comparison of permeability characteristics of the human colonic Caco-2 and rat small intestinal IEC-18 cell lines

Several human colonic carcinoma cell lines are used to study the intestinal transport of compounds in vitro. However, the major site of absorption of drugs and nutrients is the small intestine, which differs greatly from the colon in paracellular permeability. Several hydrophilic compounds, of which intestinal uptake in vivo was found, are not transported across filter-grown colonic cells in vitro. The aim of this study was to compare transport properties of the low-resistance rat small intestinal cell line IEC-18 to those of the high-resistance human colonic cell line Caco-2. After prolonged culture of Caco-2 and IEC-18 on Transwell polycarbonate filters, enzyme activity determinations revealed the presence pf sucrase-isomaltase and mature enterocyte alkaline phosphatase in Caco-2 and fetal alkaline phosphatase in IEC-18. Both cell lines formed a confluent layer as confirmed by transepithelial electrical resistance measurements (TERCaco-2=350+/-14 Omega.cm(2), TERIEC-18=55+/-4 Omega.cm(2)) and fluorescence microscopy on immunolabeled F-actin. The tight junctional protein ZO-1 is organized into cell circumscribing strands in both cell lines. Transport rates of lipophilic compounds transported transcellularly were almost similar in both cell lines, but transport rates of hydrophilic compounds transported paracellularly were clearly higher in IEC-18 cells. IEC-18 cells also allowed for a better discrimination on the basis of molecular size between several compounds which are transported paracellularly. (C) 1997 Elsevier Science B.V.