Synthesis of Noradrenaline from 3,4‐Dihydroxyphenylalanine (DOPA) and Dopamine in Adrenergic Nerves of Mouse Atrium — Effect of Reserpine, Monoamine Oxidase and Tyrosine Hydroxylase Inhibition

The in vitro synthesis of noradrenaline (NA) from 3,4‐dihydroxyphenylalanine (DOPA) and dopamine (DA) in the mouse atrium has been investigated, using isotope, subcellular distribution and histochemical techniques. Incubation of atrial tissue in 5 times 10 ‐6 M 14 C‐DOPA resulted in a formation of 14 C‐NA and 14 C‐DA at a rate of about 0.13 μg/g/hr, and 0.14 μg/g/hr respectively, whereas the same medium concentration of 3 H‐DA gave a formation of 3 H‐NA of about 0.25 μg/g/hr. The synthesis of NA and DA was found to be almost exclusively associated with the presence of adrenergic nerves, since it was considerably reduced after pretreatment with 6‐OH‐DA. Pretreatment with reserpine decreased formation of radioactive NA and DA which could be counteracted by nialamide. The effect of reserpine may be explained by inhibition of DA uptake in the amine storage granules. The antagonistic effect of nialamide is certainly due to inhibition of DA catabolism. Tyrosine hydroxylase inhibition produced by H44/68, which depleted the endogenous NA store to about 40% of normal, increased the formation of radioactive NA both from 3 H‐DA and 14 C‐DOPA. This may in part be explained by decreased competition of the endogenous precursor DA for DA‐β‐hydroxylase but also in part by increased storage sites available for newly formed NA.