TY - JOUR T1 - End-Product Inhibition of Tyrosine Hydroxylase as a Possible Mechanism for Regulation of Norepinephrine Synthesis JF - Molecular Pharmacology JO - Mol Pharmacol SP - 549 LP - 555 VL - 3 IS - 6 AU - SYDNEY SPECTOR AU - ROBERT GORDON AU - ALBERT SJOERDSMA AU - SIDNEY UDENFRIEND Y1 - 1967/11/01 UR - http://molpharm.aspetjournals.org/content/3/6/549.abstract N2 - 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. ER -