Characterization of drug transport through tight-junctional pathway in Caco-2 monolayer: comparison with isolated rat jejunum and colon.
Drug transport through the tight-junctional pathway in Caco-2 monolayer was studied by examining the relationship between its permeability to hydrophilic drugs and membrane conductance. Compared with the rat isolated jejunum or colon, Caco-2 monolayer displayed high electrical resistance and low conductance, as well as low permeability to sulfanilic acid and FITC-dextran (M.W. 4000). However, there was a linear relationship between the drug permeability and partial Cl- ion conductance for Caco-2 monolayer, rat jejunum and colon. Hence, the permeability to those drugs per unit of Cl- conductance is similar in the three membranes, suggesting that the size (radius) of the tight-junctional pathway in the three membranes is similar. In addition, when the electrical resistance of Caco-2 monolayer was reduced to the same level as that of the jejunum or colon by pretreatment with disodium ethylenediaminetetraacetate, its permeability to FITC-dextran became significantly higher than that of other membranes. Accordingly, the high resistance and the low permeability of Caco-2 monolayer compared with rat intestinal membrane may be due to structural differences between the membranes, rather than a difference in the tightness of the junction.
Tanaka
Y
Y
Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Taki
Y
Y
Sakane
T
T
Nadai
T
T
Sezaki
H
H
Yamashita
S
S
D000818:Animals; D001692:Biological Transport; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism*; D003911:Dextrans / Q000493:pharmacokinetics; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D007365:Intercellular Junctions / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate