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Monolayers of IEC-18 cells as an in vitro model for screening the passive transcellular and paracellular transport across the intestinal barrier: Comparison of active and passive transport with the human colon carcinoma Caco-2 cell line

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Author: Versantvoort, C.H.M. · Ondrewater, R.C.A. · Duizer, E. · Sandt, J.J.M. van de · Gilde, A.J. · Groten, J.P.
Type:article
Date:2002
Institution: TNO Voeding
Source:Environmental Toxicology and Pharmacology, 3-4, 11, 335-344
Identifier: 236603
doi: doi:10.1016/S1382-6689(01)00122-3
Keywords: Caco-2 · Carrier-mediated transport · H+-di/tripeptide carrier · IEC-18 · Intestinal cell lines · MRP · P-Glycoprotein · acetylsalicylic acid · calcein · carrier protein · dinitrophenylglutathione · glucose derivative · glutathione derivative · glycoprotein P · glycylsarcosine · hydrocortisone · macrogol 4000 · mannitol · methylglucose · multidrug resistance protein · probenecid · propranolol · rhodamine 123 · salicylic acid · testosterone · unclassified drug · verapamil · vincristine · animal cell · article · cell membrane permeability · cell strain CACO 2 · cell transport · colon carcinoma · controlled study · drug transport · human · human cell · in vitro study · ion transport · model · nonhuman · priority journal · protein expression · rat · screening

Abstract

Purpose: previous studies have shown that the rat small intestinal cell line IEC-18 provides a size-selective barrier for paracellularly transported hydrophilic macromolecules. In order to determine the utility of IEC-18 cells as an in vitro model to screen the passive paracellular and transcellular components of the intestinal transport of nutrients and drugs, we have now examined the transport of GlySar (H+-coupled di/tripeptide carrier), O-methyl-D-glucose (glucose carrier), vincristine and rhodamine 123 (P-glycoprotein), and calcein and DNPSG (MRPs) and the bidirectional transport of paracellularly transported compounds. Transport of these compounds across the filter grown IEC-18 cells was compared with transport across the human colon carcinoma Caco-2 cells. Results: in IEC-18 cells, transepithelial transport of GlySar and methylglucose was as fast as the transport of mannitol, which is transported passively via the paracellular route. Whereas in Caco-2 cells, mannitol transport was much slower than the transport of GlySar and methylglucose. In contrast to Caco-2 cells, no H+-coupled transport of GlySar could be measured in IEC-18 cells. P-Glycoprotein-mediated transport was characterised in Caco-2 cells by an enhanced transport of vincristine and rhodamine 123 in the basolateral to apical direction and by the inhibition of this transport by verapamil. In IEC-18 cells, permeability of vincristine and rhodamine 123 was similar in both directions and verapamil had no effect on the transport of these compounds. Both IEC-18 and Caco-2 cells efflux the organic anions calcein and DNPSG to the apical and basolateral compartments, and this efflux could be inhibited by probenecid. Conclusions: in conclusion, no carrier-mediated transport of GlySar, methylglucose, vincristine and rhodamine 123 could be determined in IEC-18 cells in contrast to Caco-2 cells. However, both IEC-18 and Caco-2 cells showed MRP-mediated eflux system(s) in the apical and basolateral membrane. Monolayers of IEC-18 cells appear to be more suitable than monolayers of Caco-2 cells as an in vitro system to screen the passive component of the intestinal transport in a deconvoluted screening regimen, where passive transport is represented by the IEC-18 monolayer permeability and active transport is represented by monolayers of cells expressing the transport proteins heterologously. © 2002 Elsevier Science B.V. All rights reserved.