Lumen-to-cell transport, cellular accumulation, and toxicity of cadmium as ionic cadmium (Cd(2+)) 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 Cd(2+) (0.73 microM) or Cys-S-Cd-S-Cys (0.73 microM) 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. Cd(2+)-transport was temperature-dependent and was inhibited by Fe(2+), Zn(2+), and elevated concentrations of Ca(2+). 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 Zn(2+) had any effect on the rate of Cys-S-Cd-S-Cys transport.
Conclusions: When delivered to the luminal compartment, Cd(2+) appears to be capable of utilizing certain transporter(s) of Zn(2+) and some transport systems sensitive to Ca(2+) and Fe(2+). 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.
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