Secretory transport of cadmium through intestinal brush border membrane via H(+)-antiport

The effect of pH on the secretory transport of Cd through the intestinal brush border membrane was investigated using isolated rat intestinal brush border membrane vesicles (BBMV) and the Caco-2 intestinal epithelial cell line. BBMV equilibrated at pH 5.5 or 7.5 (pH(in)) were mixed with an experimental buffer at pH 5.5 or 7.5 (pH(out)) containing CdCl(2). The initial accumulation of Cd in BBMV incubated for 1 or 3 min at pH(in) 5.5 and pH(out) 7.5 (outwardly directed H(+)-gradient) was significantly higher than that at pH(in)=pH(out)=7.5, but the equilibrated Cd accumulation incubated for 30 min was marginally lower. Carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), a protonophore, diminished the increasing effect of the H(+)-gradient on the initial Cd accumulation. Caco-2 cell monolayers cultured on permeable membranes were incubated with CdCl(2) from the basolateral medium, and the transport of Cd from the basolateral to apical medium and the accumulation of Cd in the monolayers were measured. Cd transport was increased by lowering the pH of the apical medium, and was accompanied by a decrease in the Cd accumulation. Coincubation with CdCl(2) and tetraethylammonium, a typical substrate for H(+)-antiport of the renal organic cation transporter, from the basolateral medium slightly but significantly decreased the basolateral-to-apical transport of Cd, with a concomitant increase in the Cd accumulation. These findings suggest the secretory transport of Cd through the intestinal brush border membrane not only via passive diffusion but also via H(+)-antiport of the putative organic cation transporter.