Molecular homology and the luminal transport of Hg2+ in the renal proximaltubule

The aim of this study was to define mechanisms involved in the luminal upta ke of inorganic mercury in the kidney using isolated perfused straight (S-2 ) segments of the proximal tubule. When mercuric conjugates of glutathione (GSH), cysteinylglycine, or cysteine (containing Hg-203(2+)) were perfused through the lumen, the rates of luminal disappearance flux (J(D)) of inorga nic mercury were approximately 39, 53, and 102 fmol/min per mm, respectivel y. Thus, the rates of luminal uptake of mercury are greater when the mercur y is in the form of a mercuric conjugate of cysteine than in the form of a mercuric conjugate of cysteinylglycine or GSH. Addition of acivicin to the perfusate, to inhibit activity of the gamma-glutamyltransferase, caused sig nificant reductions in the J(D) for mercury in tubules perfused with mercur ic conjugates of GSH. Addition of cilastatin, an inhibitor of dehydropeptid ase-1 (cysteinylglycinase) activity, caused significant reductions in the u ptake of mercury in tubules perfused with mercuric conjugates of cysteinylg lycine. These findings indicate that a significant amount of the luminal up take of mercury, when mercuric conjugates of GSH are present in the lumen, is dependent on the activity of both gamma-glutamyltransferase and cysteiny lglycinase. Finally, the J(D) for mercury in tubules perfused with mercuric conjugates of cysteine was reduced by approximately 50% when 3.0 mM L-lysi ne or 5.0 mM cycloleucine was added to the perfusate. It is concluded that these findings indicate that at least some of the luminal uptake of mercuri c conjugates of cysteine occurs at the site of one or more amino acid trans porters via a mechanism involving molecular homology.