The initial uptake of copper by the liver in the dog.

Abstract

The initial uptake of 64Cu and serum and tissue copper levels were examined in the dog. Plasma disappearance curves, multiple indicator dilution studies of initial hepatic uptake, and constant infusion experiments were carried out, at various doses, before and after preloading with cupric acetate. Over a range of plasma concentrations of direct-reacting copper extending to levels far above those encountered under physiological circumstances, little evidence of saturation of the initial hepatic uptake was evident. The countertransport of labeled copper was produced by administering unlabeled copper. The tissue levels of copper in the liver of the normal dog were, unexpectedly, found to be comparatively high, to average 82 μg/g wet weight. Attempts to produce manyfold increases in this copper content by daily intravenous copper administration failed because the doses of copper which would have been necessary to produce the increases, doses which would not have caused major toxic effects in the rat, were lethal for the dog. This low tolerance for copper loading presumably reflects the preexisting high copper concentration in the liver, the major organ which takes up exogenously administered copper. The degree of preloading which could be achieved produced no perceptible change in initial hepatic uptake. The copper levels in the liver are of the order of those found in some patients with Wilson's disease. Despite this, none of the other abnormalities which characterize this disease have been encountered in dogs.