THE EFFECT OF TYRAMINE ON THE SYNTHESIS OF NOREPINEPHRINE

¹ Department of Pharmacology, Harvard Medical School, and Neuropharmacology Laboratory, Massachusetts Mental Health Center, Boston, Massachusetts

The effect of tyramine on the synthesis of norepinephrine has been examined in isolated atria, vasa deferentia and adrenal slices of rabbits. Tyramine inhibits total catecholamine synthesis and norepinephrine synthesis from H³-tyrosine in all three tissues. Atria appear to be most sensitive to this action of tyramine, whereas adrenal slices are least affected. The synthesis of total catecholamines from dopa is not inhibited by tyramine in concentrations which inhibit catecholamine formation from H³-tyrosine. However, norepinephrine synthesis from dopa is inhibited by tyramine and the sensitivities of the three tissues are similar to those seen when H³-tyrosine is used as precursor. Tyramine competitively inhibits purified dopamine -hydroxylase of beef adrenal. It is without significant effect on purified beef adrenal tyrosine hydroxylase. In intact tissues, tyramine, norepinephrine and -methyl-p-tyrosine inhibit both the net synthesis of catecholamines and the formation of H³-H₂O from 3,5-H³-tyrosine, indicating that these agents inhibit tyrosine hydroxylase in intact tissues. The results demonstrate that tyramine inhibits norepinephrine synthesis from tyrosine at the two hydroxylation steps. The action on dopamine -hydroxylase appears to be a direct competitive antagonism; that on tyrosine hydroxylase is indirect, possibly resulting from the release of norepinephrine from storage sites and the subsequent inhibitory effect of the catecholamine on the enzyme.