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Lumen‐to‐Cell Transport of Ionic Cd and Cys‐S‐Cd‐S‐Cys in S2 Proximal Tubular Segments
Author(s) -
Wang Yanhua,
Zalups Rudolfs K,
Barfuss Delon W
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a349-b
Subject(s) - cadmium , chemistry , cysteine , cystine , conjugate , biophysics , biochemistry , biology , enzyme , organic chemistry , mathematical analysis , mathematics
The lumen‐to‐cell transport, cellular accumulation and toxicity of ionic cadmium ( 109 Cd 2+ ) and cadmium‐cysteine conjugate (Cys‐S‐Cd‐S‐Cys) were studied in isolated‐perfused S 2 segments of the proximal tubule of the rabbit kidney. All perfusion solutions were HEPES buffered and contained 3 H‐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 Cd 2+ , 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 Cd 2+ transport was temperature dependent (22°C 78% reduction) and inhibited by verapamil (100μM 51% reduction) and high Ca 2+ 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 S 2 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.