Uptake of copper by mouse hepatocytes.

This study has investigated the uptake of copper by mouse hepatocytes. The cells gave similar results whether they were used right after isolation or maintained overnight on collagen-coated dishes. Uptake from cells in suspension followed two phases: an initial rapid binding followed by a linear uptake phase. The two phases were not so easily distinguishable in cells grown in culture where uptake was linear over the first hour. The uptake showed saturation but may not have followed simple kinetics. Histidine stimulated uptake in a concentration-dependent manner, as did some other amino acids, but copper had very little effect on histidine uptake. The process was not dependent on intracellular adenosine triphosphate (ATP), since inhibitors that substantially reduced ATP levels inside the cell did not alter copper uptake. The inhibitors, however, blocked histidine uptake to varying degrees, suggesting that copper and histidine are taken up by different pathways. The uptake was reduced markedly by N-ethyl maleimide, and preincubation of the cells with "Pronase" resulted in a decrease of uptake. A model for the uptake of copper by hepatocytes that incorporates the data presented in this paper with that produced by earlier workers is suggested.