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 intes tinal transport of compounds in vitro. However, the major site of abso rption of drugs and nutrients is the small intestine, which differs gr eatly from the colon in paracellular permeability. Several hydrophilic compounds, of which intestinal uptake in vivo was found, are not tran sported across filter-grown colonic cells in vitro. The aim of this st udy was to compare transport properties of the low-resistance rat smal l intestinal cell line IEC-18 to those of the high-resistance human co lonic cell line Caco-2. After prolonged culture of Caco-2 and IEC-18 o n Transwell polycarbonate filters, enzyme activity determinations reve aled 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 el ectrical resistance measurements (TERCaco-2=350+/-14 Omega.cm(2), TERI EC-18=55+/-4 Omega.cm(2)) and fluorescence microscopy on immunolabeled F-actin. The tight junctional protein ZO-1 is organized into cell cir cumscribing 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 parac ellularly were clearly higher in IEC-18 cells. IEC-18 cells also allow ed for a better discrimination on the basis of molecular size between several compounds which are transported paracellularly. (C) 1997 Elsev ier Science B.V.