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Copper-Deficient Mice Have Higher Cardiac Norepinephrine Turnover^1,2

Department of Biochemistry, School of Medicine, University of Minnesota, Duluth 55812

Norepinephrine metabolism was investigated in 6-wk-old male Swiss albino copper-deficient and copper-supplemented mice. Beginning 4 d after birth of pups, dams were fed a diet low in copper (Cu) (0.4 mg/kg) and offspring were weaned to this diet at 21 d of age. Half the dams and their respective offspring received Cu (20 µg/ml) in the drinking water (+Cu) and served as controls. Unsupplemented offspring (-Cu) had lower liver Cu levels, exhibited anemia, and had increased heart weights but normal body weights compared to +Cu mice. Urinary output of norepinephrine and dopamine was higher, whereas output of creatinine and epinephrine was not different in -Cu mice compared to +Cu mice. Both fractional and calculated turnover of norepinephrine following inhibition of tyrosine 3-monooxygenase by -methyl-p-DL-tyrosine methyl ester (-MT) was higher in hearts from -Cu mice than in those from +Cu mice. Hearts and spleens from -Cu mice appeared to have higher tyrosine 3-monooxygenase activity as judged by increasing rates of L-dihydroxyphenylalanine accumulation following injection of m-hydroxybenzylhydrazine (NSD-1015), an inhibitor of aromatic amino acid decarboxylase. Turnover rates of norepinephrine for cerebellum were not different between +Cu and -Cu mice. Loss of norepinephrine from adrenal glands of mice injected with -MT was not observed in the 8-h period studied. The smaller norepinephrine pool observed in organs of -Cu mice may have resulted from lower synthesis due to limiting dopamine-ß-monooxygenase activity and to higher turnover.

KEY WORDS: • copper • mice • catecholamines • norepinephrine turnover

¹ Research supported in part by Public Health Service grant HD 20975 and Minnesota Medical Foundation grant DMRF-30-84.

² Presented in part at the 73rd Annual Meeting of the Federation of American Societies for Experimental Biology, New Orleans, Louisiana, March 1989 [GROSS, A. M. & PROHASKA, J. R. (1989) Copper-deficient mice have higher cardiac norepinephrine turnover. FASEB J. 3: A1062].

Manuscript received 30 May 1989. Revision accepted 15 September 1989.