title: Characterization of basolateral-to-apical transepithelial transport of cadmium in intestinal TC7 cell monolayers.
abstract: Cadmium (Cd) is a toxic metal with an extremely long half-life in humans. The intestinal absorption of Cd has been extensively studied but the role the intestinal epithelium may play in metal excretion has never been considered. The basolateral (BL)-to-apical (AP) transepithelial transport of Cd was characterized in TC7 human intestinal cells. Both AP and BL uptakes varied with days in culture, and BL uptake was twofold higher compared to AP in differentiated cultures. A 50% increase in the BL uptake of 0.5 μM (109)Cd was observed at pH 8.5 in a chloride but not nitrate medium, suggesting the involvement of a pH-sensitive mechanism of transport for chloro-complexes. Fe and Zn inhibited the BL uptake of Cd whereas complexation by albumin had no effect, but the stimulatory effect of pH 8.5 was lost in the presence of albumin. The BL uptake of [(3)H]-MPP(+) and (109)Cd were both inhibited by decynium22 without reciprocal inhibition. MRP2 and MDR1 mRNA levels increased as a function of days in culture. A 25 and 20% decrease in the cellular AP efflux of Cd was observed in the presence of verapamil and probenecid, respectively. In cells treated with BSO, which lowered by 26% the total cellular thiol content, the inhibitory effect of verapamil increased, whereas that of probenecid decreased. These results reveal the existence of a decynium22-sensitive mechanism of transport for Cd at the BL membrane, and suggest the involvement of MDR1 and MRP2 in cellular Cd efflux at the AP membrane. It is conceivable that the intestinal epithelium may contribute to Cd blood excretion.
authors.affiliation: Département des sciences biologiques, Centre TOXEN, Université du Québec à Montréal, C.P. 8888, Succursale Centre-ville, Montréal, QC, H3C 3P8, Canada.
authors.forename: Pascale
authors.initials: P
authors.lastname: Carrière
authors.forename: Marc
authors.initials: M
authors.lastname: Mantha
authors.forename: Sophie
authors.initials: S
authors.lastname: Champagne-Paradis
authors.forename: Catherine
authors.initials: C
authors.lastname: Jumarie
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002104:Cadmium / Q000378:metabolism*; D002106:Cadmium Radioisotopes / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016764:Cell Polarity; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000166:cytology*; D011804:Quinolines / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D002106:Cadmium Radioisotopes; D011804:Quinolines; D002104:Cadmium; C100254:pseudoisocyanine