Amino Acid Transporters Involved in Luminal Transport of Mercuric Conjugates of Cysteine in Rabbit Proximal Tubule

Abstract

The primary aim of the present study was to test the hypothesis that amino acid transport systems are involved in absorptive transport of dicysteinylmercury (cysteine-Hg-cysteine). Luminal disappearance flux [J_D, fmol min⁻¹ (mm tubular length)⁻¹] of inorganic mercury (Hg²⁺), in the form of dicysteinylmercury, was measured in isolated perfused S₂ segments with various 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 fluid contained 20 μM dicysteinylmercury. Replacing Na⁺ in both the bathing and perfusing solutions withN-methyl-d-glucamine reduced theJ_D of Hg²⁺ by about 40%. Nine amino acids and two amino acid analogs were coperfused individually (at millimolar concentrations) with dicysteinylmercury. The amino acids and amino acid analogs that had the greatest effect on theJ_D of Hg²⁺ werel-cystine, l-serine, l-histidine,l-tryptophan, and 2-(−)-endoamino-bicycloheptane-2-carboxylic acid. The greatest reduction (76%) in the total J_D of Hg²⁺ occurred when l-cystine was coperfused with dicysteinylmercury in the presence of Na⁺. Overall, the current findings indicate that Hg²⁺ is transported from the lumen into proximal tubular epithelial cells via 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-affinity l-cystine, B⁰, and ASC systems and the Na⁺-independent L-system. Furthermore, the transport data obtained whenl-cystine was added to the luminal fluid indicate strongly that dicysteinylmercury is likely transported as a molecular homolog ofl-cystine.