Renal Organic Anion Transport System: A Mechanism for the Basolateral Uptake of Mercury-Thiol Conjugates along the Pars Recta of the Proximal Tubule

The basolateral handling of 20 μM inorganic mercury (Hg2+), in the form of mercuric conjugates of cysteine (Cys), N-acetylcysteine (NAC), or glutathione (GSH), was studied in isolated perfused S2 segments of the rabbit proximal tubule. One of the primary aims of the present study was to determine in a direct manner whether basolateral uptake of Hg++ occurs in the pars recta of the proximal tubule and, more importantly, whether the p-aminohippurate-sensitive (PAH) organic anion transport system is involved in this process. Basolateral uptake and accumulation of Hg++ occurred when the basolateral membrane of the tubular segments was exposed to mercuric conjugates of Cys, NAC, or GSH. Net basolateral uptake of Hg++ was more than twice as great in the tubules exposed to mercuric conjugates of Cys or NAC than in the tubules exposed to mercuric conjugates of GSH, indicating that mercuric conjugates of Cys or NAC are transported more efficiently than mercuric conjugates of GSH. When PAH (1 mM) was added to the basolateral compartment (bath) surrounding a perfused S2 segment, the net uptake of Hg++ (in the form of the mercuric conjugates) was reduced by 60–70%. In addition, when glutarate (4 mM), a transportable substrate for both the sodium-dependent dicarboxylate transporter and the dicarboxylate/organic anion exchanger (OAT1), was added to the basolateral compartment, there was a significant reduction in the uptake and accumulation of Hg++ in the form of mercuric conjugates of Cys. Overall, these data indicate that Hg++, in the form of biologically relevant mercuric conjugates of Cys, NAC, or GSH, is taken up significantly at the basolateral membrane of pars recta segments of the proximal tubule, and this uptake is mediated mainly by the actions of the PAH-sensitive organic anion transport system.