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 μM) or Cys-S-Cd-S-Cys (0.73 μM) was perfused through the lumen of S₂ 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 on its form. These findings provide a focus for future studies of Cd absorption in the proximal tubule.