RENAL TRANSPORT-SYSTEMS FOR ORGANIC-ANIONS AND CATIONS IN CADMIUM-EXPOSED RATS

To evaluate the effect of cadmium intoxication on renal transport syst ems for organic anions and cations, transport of p-aminohippurate (PAH ) and tetraethylammonium (TEA) were studied in renal cortical plasma m embrane vesicles isolated from cadmium-intoxicated rats. Cadmium intox ication was induced by daily injections of CdCl2 (2 mg Cd/kg.day sc) f or 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 attenuat ion of Na+-dependent, alpha-ketoglutarate (alpha KG)-driven PAH uptake in the basolateral membrane vesicle (BLMV), and this was due to a red uction in V-max and not K-m. The Na+- alpha KG symport activity of the BLMV was not affected by 2-week cadmium treatment, but it was signifi cantly inhibited by 3-week cadmium treatment. On the other hand, the a lpha KG-PAH antiport activity of the BLMV appeared to be markedly supp ressed in 2-week as well as 3-week cadmium-treated animals. The cadmiu m treatment inhibited the proton gradient-dependent TEA transport in t he brush-border membrane vesicle (BBMV), and this was associated with a reduction in V-max with no change in K-m. These results indicate tha t cadmium exposures may impair the capacities for organic anion transp ort in the proximal tubular basolateral membrane and organic cation tr ansport in the luminal membrane. The cadmium effect on organic anion t ransport is attributed mainly to an inhibition of dicarboxylate-organi c anion antiport system. (C) 1998 Academic Press.