Cadmium uptake by isolated rat hepatocytes

Isolated hepatocytes have been employed to investigate the uptake of the heavy metal cadmium (¹⁰⁹Cd). A rapid initial phase of uptake was followed by a second slower phase, both of which exhibited a linear relationship between velocity of uptake and substrate concentration. The presence of potassium cyanide (1 mm) and carbonyl cyanide-m-chlorophenyl hydrazone (2 μm) did not cause any change in the uptake of Cd (200 μm). This suggests that the uptake of Cd into isolated hepatocytes is not an active process. Incubation of 10 μm Cd in the presence of zinc (50 and 130 μm) produced a decrease in the velocity of uptake of only the first phase. Pretreatment of rats with zinc, which elevates hepatic metallothionein, resulted in isolated hepatocytes which showed a greater uptake rate for the second phase when compared to hepatocytes isolated from control rats. The results therefore demonstrate that uptake of Cd by isolated rat hepatocytes is a biphasic response in which at least part of the first phase appears to be carrier mediated with no indication of involvement of a carrier in the second phase of uptake. This second phase may be related to binding of Cd to intracellular components, since elevation of hepatic metallothionein was found to increase the uptake velocity of only this phase.