Inhibition of intestinal copper absorption by divalent cations and low-molecular-weight ligands in the rat

l-histidine (His) has been shown to enhance the inhibitory effect of zinc on intestinal copper absorption. This study was aimed at examining whether this effect of His was also extended to the interactions of other divalent cations: ferrous iron, tin, and cobalt, using an in vivo perfusion system in rats. Copper absorption and intestinal content of this element significantly decreased in the presence of 2 mM His and ferrous iron. Iron accumulation was greater when His was present than when omitted. A fivefold excess of tin inhibited copper absorption only when His was present. Citrate, at the same concentration as His, had no effect on copper absorption, but hepatic copper levels were increased, as compared to the absence of either His or citrate. Addition of 0.5 or 1.0 mM cobaltous salt plus His resulted in a sharp decrease in copper intestinal absorption, with an increase in intestinal tissue retention. These results confirm earlier findings with zinc and His, and suggest that a general phenomenon, either accelerating the removal of copper from the intestinal lumen or increasing, the retention of this element by the intestinal tissue, is a common feature of the interaction between cations of similar electronic configuration to copper and a high-affinity ligand, such as His.