Uptake of copper from the bloodstream and its relation to induction of metallothionein synthesis in the rat

1. Female rats of the Wistar strain (12 weeks old; body wt, 200 g) were injected intravenously with a single dose of cupric chloride (0.8 mg Cu/kg body wt) and the uptake of copper (Cu) by the liver and kidneys was determined in relation to the disappearance of Cu from the bloodstream and the excretion to bile and urine. 2. Serum Cu level decreased rapidly within 30 min and then returned slowly to the control level by 3 hr post-injection, while the hepatic uptake of Cu continued linearly after the injection up to 4 hr post-injection. 3. The time lag between the disappearance of Cu from the blood serum and the uptake of Cu by the liver was not explained by the temporal distribution to red blood cells or by the enterohepatic circulation. 4. Cu taken up by the liver and distributed to its soluble fraction was bound to metallothionein, suggesting that the uptake of Cu by the liver depends on the induction of metallothionein synthesis. 5. Rapid uptake of Cu by the kidneys was observed at the beginning, which may indicate the role of the existing metallothionein in the control rat.