Potential mechanisms involved in the absorptive transport of cadmium in isolated perfused rabbit renal proximal tubules

Lumen-to-cell transport, cellular accumulation. and toxicity of cadmium as ionic cadmium (Cd2+) or as the L-cysteine (Cys) or D,L-homocysteine (Hcy) S-conjugate of cadmium (Cys-S-Cd-S-Cys, Hcy-S-Cd-S-Hcy) were studied in isolated, perfused rabbit proximal tubular segments When Cd2+ (0 73 mu M) or Cys-S-Cd-S-Cys (0.73 mu M) was perfused through the lumen of S-2 segments of the proximal tubule, no visual evidence of cellular pathological changes was detected during 30 min of study. Cd2+-transport was temperature-dependent and was inhibited by Fe2+, Zn2+, and elevated concentrations of Ca2+. Luminal uptake of Cys-S-Cd-S-Cys was also temperature-dependent and was inhibited by the amino acids L-cystine and L-arginine, while stimulated by L-methionine Neither L-aspartate, L-glutamate, the synthetic dipeptide. Gly-Sar nor Zn2+ had any effect on the rate of Cys-S-Cd-S-Cys transport. Conclusions When delivered to the luminal compartment, Cd2+ appears to be capable of utilizing certain transporter(s) of Zn2+ and some transport systems sensitive to Ca2+ and Fe2+. In addition. Cys-S-Cd-S-Cys and Hcy-S-Cd-S-Hcy appear to be transportable substrates of one or more amino acid transporters participating in luminal absorption of the amino acid L-cystine (Such as system b(0)) These findings indicate that multiple mechanisms could be involved in the luminal absorption of cadmium (Cd) in proximal tubular segments depending oil its form. These findings provide a focus for future studies of Cd absorption in the proximal tubule (C) 2009 Elsevier Ireland Ltd All rights reserved