Lumen‐to‐Cell Transport of Ionic Cd and Cys‐S‐Cd‐S‐Cys in S2 Proximal Tubular Segments

Abstract

The lumen-to-cell transport, cellular accumulation and toxicity of ionic cadmium (109Cd2+) and cadmium-cysteine conjugate (Cys-S-Cd-S-Cys) were studied in isolated-perfused S2 segments of the proximal tubule of the rabbit kidney. All perfusion solutions were HEPES buffered and contained 3H-L-glucose as a volume and leak marker and 250 nM FD & C Green dye as a vital dye. When either ionic cadmium, 0.73μM Cd2+, or 0.73μM cadmium-cysteine conjugate (Cys-S-Cd-S-Cys) containing solution was perfused through the lumen of the tubule there was no visual evidence of toxicity such as seen with mercury and mercury conjugates; blebbing of the luminal membrane, cellular vital dye uptake, and cellular swelling. Ionic Cd2+ transport was temperature dependent (22°C 78% reduction) and inhibited by verapamil (100μM 51% reduction) and high Ca2+ concentrations (2.6mM 65% reduction). The cadmium conjugate (Cys-S-Cd-S-Cys) transport was also temperature dependent (22°C 70% reduction) and inhibited by the amino acids L-cystine, L-arginine, and L-aspartate, (46% L-cystine >, 41% L-arginine>, and > 24% L-aspartate). We conclude that cadmium can be transported at the luminal membrane of the S2 segment of the proximal tubule by multiple mechanisms, depending on the form in which it is presented to membrane. Ionic cadmium appears to be transported by calcium channels while cadmium conjugate of L-cysteine appears to be transported by several different amino acid transport systems.