THE PHYSIOLOGIC DISPOSITION AND METABOLISM OF NOREPINEPHRINE IN IMMUNOSYMPATHECTOMIZED ANIMALS

¹ Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland

The uptake and metabolism of H3-norepinephrine was examined in immunosympathectomized (IS) rats and mice. IS affected the uptake of H³-norepinephrine in different tissues to markedly different extents. In the rat heart and spleen, H³-norepinephrine uptake was reduced to less than 10% of normal; H³-norepinephrine uptake was 30 to 60% of normal in salivary glands, liver and intestine, and was unaffected in uterus, urinary bladder, brain and seminal vesicles. A significant increase in H³-norepinephrine uptake was found its IS vas deferens. In general, the reduction in the accumulation of H³-norepinephrine in various IS tissues paralleled the reduction in the endogenous catecholamine content of these tissues. A significant increase in the serotonin content of IS mouse intestine was found. After intravenous injection in the mouse, H³-norepinephrine was metabolized more rapidly in IS animals than in normal. In all tissues of IS rats there was a relative increase in the accumulation of H³-metabolites of norepinephrine, mainly accounted for by an increased content of the O-methylated metabolite, normetanephrine. However, there were no changes in the activity of catechol-O-methyl transferase in IS mouse tissues. A decreased monoamine oxidase activity was found in IS salivary glands, but no differences in the activity of this enzyme were observed in other IS tissues. Aromatic L-amino acid decarboxylase activity was decreased in IS heart, salivary glands and intestine, but not in liver or brain. The -hydroxylation of H3--methyltyramine was impaired in IS tissues, suggesting a decreased dopamine--oxidase activity. The rate of turnover of adrenal medullary catecholamines was more than twice as fast in IS mice as in normals. Repeated injections of antiserum during the first week after birth failed to abolish H³-norepinephrine uptake completely in any rat tissue. The decreases in norepinephrine uptake in the rat heart produced by various amounts of antiserum can be used as a sensitive bioassay procedure for the estimation of nerve growth factor antiserum.

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