Subcellular Distribution of3H‐noradrenaline in Adrenergic Nerves of Mouse Atrium — Effect of Reserpine, Monoamine Oxidase and Tyrosine Hydroxylase Inhibition

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Abstract
The subcellular distribution of exogenously administered3H‐noradrenaline in adrenergic nerves of mouse atria after pretreatment with nialamide, reserpine and nialamide, or the methylester ofa‐methyl‐p‐tyrosine (H44/68) has been investigated. Parallel fluorescence histochemical studies have been performed. Both reserpine and H44/68 cause a pronounced decrease in the endogenous noradrenaline stores. The subcellular distribution was practically identical in untreated, nialamide‐pretreated and H44/68‐pretreated animals; approximately 30%3H‐noradrenaline was recovered in the particulate fraction which in all probability contains the amine storage granules. In the reserpine‐nialamide pretreated mice, however, most of the3H‐noradrenaline was found in the supernatant iraction, and about 10 % in the particulate fraction. These studies thus confirm earlier investigations that reserpine is a potent inhibitor of the noradrenaline uptake in the amine storage granules, although there is a small reserpineresistant uptake. Furthermore, after tyrosine hydroxylase inhibition both the ‘membrane pump’ and the granular uptake mechanism seem to operate. The morphological studies disclosed differences in the adrenergic nerves when the noradrenaline taken up is mainly granularly or extragranularly stored, since the varicosities are in the former case distinct and the latter case less distinct, while the pre‐terminals are more prominent. Methodological studies of the homogenization procedure for subcellular distribution studies have also been performed, the results of which are discussed in view of the experimental data obtained.It is now well established, based on both biochemical and electronmicroscopic evidence. that the peripheral adrenergic transmitter NAIis mainly stored in special intraneuronal storage granules (Euler and Hillarp 1956. Schümann 1958. Camps and Shideman 1962. Potter and Axelrod 1962, Lundborg 1967, Hokfelt 1969). Exogenously administered NA is rapidly taken up by the axonal membrane of the adrenergic neuron and subsequently incorporated into the storage granules, mainly by means of an ATP‐Mg++‐dependent uptake mechanism. This latter process can be efficiently‐blocked by reserpine (Carlssonet al.1963, Euler and Lishajko 1963.