Amino acid transporters involved in luminal transport of mercuric conjugates of cysteine in rabbit proximal tubule

The primary aim of the present study was to test the hypothesis that amino acid transport systems are involved in absorptive transport of dicysteinylm ercury (cysteine-Hg-cysteine). Luminal disappearance flux [J(D), fmol min(- 1) (mm tubular length)(-1)] of inorganic mercury (Hg2+), in the form of dic ysteinylmercury, was measured in isolated perfused S-2 segments with variou s amino acids or amino acid analogs in the luminal compartment under one of two conditions, in the presence or absence of Na+. The control perfusion f luid contained 20 muM dicysteinylmercury. Replacing Na+ in both the bathing and perfusing solutions with N-methyl-D-glucamine reduced the J(D) of Hg2 by about 40%. Nine amino acids and two amino acid analogs were coperfused individually (at millimolar concentrations) with dicysteinylmercury. The am ino acids and amino acid analogs that had the greatest effect on the J(D) o f Hg2+ were L-cystine, L-serine, L-histidine, L-tryptophan, and 2-(-)-endoa mino-bicycloheptane-2-carboxylic acid. The greatest reduction (76%) in the total J(D) of Hg2+ occurred when L-cystine was coperfused with dicysteinylm ercury in the presence of Na+. Overall, the current findings indicate that Hg2+ is transported from the lumen into proximal tubular epithelial cells v ia amino acid transporters that recognize dicysteinylmercury. In addition, the data indicate that multiple amino acid transporters are involved in the luminal uptake of dicysteinylmercury, including the Na+-dependent low-affi nity L-cystine, B-O, and ASC systems and the Na+-independent L-system. Furt hermore, the transport data obtained when L-cystine was added to the lumina l fluid indicate strongly that dicysteinylmercury is likely transported as a molecular homolog of L-cystine.