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 dicysteinylmercury (cysteine-Hg-cysteine). Luminal disappearance flux [JD, fmol x 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 microM dicysteinylmercury. Replacing Na+ in both the bathing and perfusing solutions with N-methyl-D-glucamine reduced the JD 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 the JD of Hg2+ were L-cystine, L-serine, L-histidine, L-tryptophan, and 2-(-)-endoamino-bicycloheptane-2-carboxylic acid. The greatest reduction (76%) in the total JD 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, B(0), and ASC systems and the Na+-independent L-system. Furthermore, the transport data obtained when L-cystine was added to the luminal fluid indicate strongly that dicysteinylmercury is likely transported as a molecular homolog of L-cystine.
Cannon
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Biology Department, Georgia State University, Atlanta, Georgia 30303, USA.
Zalups
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Barfuss
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D026905:Amino Acid Transport Systems; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008628:Mercury / Q000378:metabolism; D009941:Organomercury Compounds / Q000378:metabolism*; D011817:Rabbits; D012964:Sodium / Q000502:physiology; D013237:Stereoisomerism
D026905:Amino Acid Transport Systems; D002352:Carrier Proteins; D009941:Organomercury Compounds; D012964:Sodium; D008628:Mercury; D008239:Lysine; D003545:Cysteine