In vivo inhibition of serum dopamine-beta-hydroxylase by CaNa2 EDTA injection.
1. In humans CaNa2EDTA increases urinary excretion of lead as well as that of essential metals such as zinc, ferrum and manganese but not that of copper. 2. We studied the effect of CaNa2EDTA injection on serum dopamine-beta-hydroxylase, a copper-dependent enzyme, in three male lead welders hospitalized for suspected lead poisoning. 3. Injection of CaNa2EDTA (1000 mg i.v.) resulted in rapid reduction of serum dopamine-beta-hydroxylase activity which returned to normal level within 24 hours. 4. Copper sulphate (8 microns) but not ethylmaleimide (10 mM) restored in vitro serum dopamine-beta-hydroxylase activity to pre-dosing values which indicates that CaNa2EDTA inhibits dopamine-beta-hydroxylase by removing copper from the enzyme. 5. An inverse dose effect relationship between injected CaNa2EDTA and residual serum dopamine-beta-hydroxylase activity was observed. 6. In spite of the reported lack of changes in copper serum concentration, CaNa2EDTA significantly affects the activity of a copper-dependent enzyme in the serum. 7. As CaNa2EDTA is currently the drug of choice for the treatment of asymptomatic lead poisoning in children, the effect of CaNa2EDTA on copper-enzymes requires further investigation.
De Paris
P
P
Istituto di Medicina del Lavoro, University of Padova, Italy.
Caroldi
S
S
D000328:Adult; D003300:Copper / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors* / Q000097:blood*; D004492:Edetic Acid / Q000494:pharmacology*; D006801:Humans; D007855:Lead Poisoning / Q000378:metabolism; D008297:Male
D003300:Copper; D004492:Edetic Acid; D004299:Dopamine beta-Hydroxylase