Renal Transport Systems for Organic Anions and Cations in Cadmium-Exposed Rats

Abstract

To evaluate the effect of cadmium intoxication on renal transport systems for organic anions and cations, transport ofp-aminohippurate (PAH) and tetraethylammonium (TEA) were studied in renal cortical plasma membrane vesicles isolated from cadmium-intoxicated rats. Cadmium intoxication was induced by daily injections of CdCl2(2 mg Cd/kg · day sc) for 2–3 weeks. Renal plasma membrane vesicles were prepared by Percoll gradient centrifugation and magnesium precipitation method. Vesicular uptake of substrate was determined by rapid filtration technique using Millipore filter. The cadmium treatment resulted in a marked attenuation of Na+-dependent, α-ketoglutarate (αKG)-driven PAH uptake in the basolateral membrane vesicle (BLMV), and this was due to a reduction inVmaxand notKm. The Na+-αKG symport activity of the BLMV was not affected by 2-week cadmium treatment, but it was significantly inhibited by 3-week cadmium treatment. On the other hand, the αKG-PAH antiport activity of the BLMV appeared to be markedly suppressed in 2-week as well as 3-week cadmium-treated animals. The cadmium treatment inhibited the proton gradient-dependent TEA transport in the brush-border membrane vesicle (BBMV), and this was associated with a reduction inVmaxwith no change inKm. These results indicate that cadmium exposures may impair the capacities for organic anion transport in the proximal tubular basolateral membrane and organic cation transport in the luminal membrane. The cadmium effect on organic anion transport is attributed mainly to an inhibition of dicarboxylate–organic anion antiport system.