ROLE OF EXTRACELLULAR THIOLS IN ACCUMULATION AND DISTRIBUTION OF INORGANIC MERCURY IN RAT RENAL PROXIMAL AND DISTAL TUBULAR CELLS

Distribution of inorganic mercury (Hg) into both acid-soluble and prot ein-bound fractions of proximal tubular (PT) cells from the rat increa sed with increasing concentrations of Hg up to 10 mu M. Little correla tion was found between subcellular distribution of Hg and dose in dist al tubular (DT) cells. Cellular accumulation of Hg was rapid, reaching equilibrium values by 10 to 15 min. Cellular content of Hg was signif icantly higher in PT cells than in DT cells at 1 mu M Hg. To assess th e effect of extracellular thiols on the intracellular accumulation of Hg, PT and DT cells were coincubated with Hg and cysteine, glutathione (GSH), bovine serum albumin (BSA) or 2,3-dimercapto-1-propanesulfonic acid (DMPS) in a 4:1 thiol:Hg molar ratio. Coexposure with Hg and cys teine increased intracellular accumulation of Hg in PT cells at 0.1 mu M Hg relative to exposure to Hg alone, consistent with an Hg-cysteine conjugate being a transport form of Hg. In contrast, coexposure with Hg and BSA or DMPS markedly decreased accumulation of Hg relative to c ells exposed to Hg alone in both cell types. Coexposure with Hg and GS H also decreased accumulation of Hg relative to exposure to Hg alone, but the decrease was less than coexposure with either BSA or DMPS, sug gesting that either an Hg-GSH complex may be a transport form or that some of the Hg-GSH complexes were degraded to Hg-cysteine by the actio n of brush-border membrane enzymes. These results demonstrate that ext racellular thiols markedly alter the renal accumulation of Hg and sugg est that some Hg-thiol conjugates may be important physiological trans port forms of Hg in the kidney.