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Molecular Pharmacology, Vol 3, 549-555, Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics
1 Experimental Therapeutics Branch and the Laboratory of Clinical Biochemistry,
National Heart Institute, National Institutes of Health,
Bethesda, Maryland 20014
The present study was undertaken to evaluate the influence of endogenous norepinephrine content on the rate of norepinephrine synthesis in vivo. Tissue levels of norepinephrine were increased in guinea pigs by administration of a monoamine oxidase inhibitor and tyrosine-14C and DOPA-3H were used to measure norepinephrine synthesis. In brain and heart when norepinephrine levels were increased 2- to 3-fold, conversion of tyrosine-14C to norepinephrine was decreased markedly. When tyrosine hydroxylase was bypassed by administering DOPA-3H, conversion to norepinephrine was actually increased. These findings lend support to the hypothesis that norepinephrine synthesis is regulated by a mechanism of end-product inhibition at the tyrosine hydroxylase step.
Submitted on June 15, 1967
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