Comparison of cadmium uptakes from apical and basolateral membranes of LLC-PK1 cells.
Cadmium (Cd) uptake from the apical and basolateral membranes was investigated in LLC-PK1 cells grown as a monolayer on a permeable membrane. The cells were incubated at 37 degrees C for 1 hr with 1 microM CdCl2 from either the apical or the basolateral side. The accumulation of Cd from the apical side was 23% higher than that from the basolateral side. However, the translocation of Cd from the apical to the basolateral side and vice versa were similar. Cytotoxicity, as evaluated by transepithelial electrical resistance (TER), was undetectable at 1 microM Cd concentration. The preincubation of cells with carbonylcyanide p-(trifluoromethoxy)-phenylhydrazone (a metabolic inhibitor) and ouabain (a Na+/K+ - ATPase inhibitor) or coincubation with Cd and 2,4-dinitrophenol (a metabolic inhibitor) decreased both the accumulation (16-24%) and the translocation of Cd (22-25%) from the apical side, but not from the basolateral side. Incubation of cells with 50 and 75 microM CdCl2 for 1 hr resulted in 52-112% higher accumulation and translocation of Cd from the basolateral than from the apical side. The TER decreased at high Cd concentrations, suggesting that Cd concentrations of 10 microM and higher were cytotoxic. It is concluded that uptake of Cd from both the apical and the basolateral membranes represents passive diffusion. Additionally, under nontoxic conditions, about 20% of the Cd taken up at the apical membrane reflects carrier-mediated transport involving sodium ion- and energy-dependent processes; this accounts for higher accumulation through the apical membrane.
Kimura
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Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan.
Endo
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Sakata
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D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics*; D019256:Cadmium Chloride; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002712:Chlorides / Q000493:pharmacokinetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018374:LLC-PK1 Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010042:Ouabain / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013552:Swine; D013696:Temperature; D015032:Zinc / Q000494:pharmacology
D002712:Chlorides; D004791:Enzyme Inhibitors; D002104:Cadmium; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D015032:Zinc; D019256:Cadmium Chloride