Effects of deoxycholate on the transepithelial transport of sucrose and horseradish peroxidase in filter-grown Madin-Darby canine kidney (MDCK) cells.
Madin-Darby canine kidney (MDCK) epithelial cells grown on microporous polycarbonate filters were used as a model system to investigate the mechanisms of enhancement by deoxycholate in the transepithelial transport of horseradish peroxidase (HRP) and 14C-sucrose. Deoxycholate at 0.025% had no effect on the transepithelial electrical resistance (TEER); a fivefold enhancement on the transepithelial transport of HRP, but not on that of 14C-sucrose, was observed. Deoxycholate at 0.05% induced a reversible decrease of TEER; a 2- and 50-fold enhancement on the transepithelial transport of 14C-sucrose and HRP, respectively, was observed. At 0.1%, deoxycholate induced an irreversible decrease in TEER and the epithelial barrier in the cell monolayer was completely eliminated. A 3.3-fold increase in cellular uptake in HRP, but not in 14C-sucrose, was also observed in the presence of 0.025% deoxycholate. The increase in cellular uptake was abolished when HRP was conjugated to polylysine. These results suggest that deoxycholate can increase the transepithelial transport by at least two different mechanisms, i.e., a transcellular pathway, possibly due to the enhancement of cellular uptake of selective molecules, and a nonselective paracellular pathway, due to the loosening of tight junctions by deoxycholate at higher concentrations.
Lin
Y J
YJ
Division of Pharmaceutics, University of Southern California School of Pharmacy, Los Angeles 90033.
Shen
W C
WC
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004285:Dogs; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics*; D007365:Intercellular Junctions / Q000187:drug effects; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D011107:Polylysine / Q000493:pharmacokinetics / Q000031:analogs & derivatives; D013395:Sucrose / Q000493:pharmacokinetics*
C061731:horseradish peroxidase-polylysine conjugate; D003840:Deoxycholic Acid; D011107:Polylysine; D013395:Sucrose; D006735:Horseradish Peroxidase