Lack of luminal or basolateral uptake and transepithelial transport of mercury in isolated perfused proximal tubules exposed to mercury-metallothionein.

Abstract

The lumen-to-bath and bath-to-lumen transport, cellular uptake, and toxicity of inorganic mercury bound to metallothionein (203Hg-MT) were studied in isolated perfused S1, S2, and S3 segments of the renal proximal tubule of rabbits. Evidence of very mild toxicity was displayed in some of the segments perfused through the lumen with 18.4 microM inorganic mercury in the form of Hg-MT. The toxic response was restricted primarily to mild swelling of the epithelial cells localized at the end of the tubular segments where the perfusion pipette was inserted into the lumen. The cells in the proximal portions of perfused S2 segments appeared to be most severely affected in that a few blebs would on occasion come off the epithelial cells. Mild cellular swelling was also observed in some S2 and S3 segments that were exposed to 18.4 microM inorganic mercury in the form of Hg-MT in the bath. The swelling was more generalized, involving all the epithelial cells along the perfused segment. Very little, or no, measurable lumen-to-bath or bath-to-lumen transport of Hg as Hg-MT could be detected in any of the 3 perfused segments of the proximal tubule during 40-45 min of perfusion. The complex of Hg-MT appeared to behave in a manner similar to that of the volume marker [3H]-L-glucose. The lack of tubular transport of Hg as Hg-MT was confirmed by little or no measurable uptake and accumulation of inorganic mercury in the tubular epithelial cells. Thus, our findings indicate that the Hg-MT complex is not taken up avidly in isolated perfused S1, S2, or S3 segments of the proximal tubule.