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

Abstract

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+ (0.73μM) or Cys-S-Cd-S-Cys (0.73μM) was perfused through the lumen of S2 segments of the proximal tubule, no visual evidence of cellular pathological changes was detected during 30min 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 b0,+). 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.