Failure of 6-hydroxynoradrenaline to produce degeneration of catecholamine neurons

Abstract

The effects of 6-hydroxynoradrenaline on the fluorescence morphology, uptake and retention of 3H-amine in catecholamine neurons of the mouse have been investigated. 6-Hydroxynoradrenaline did not cause any changes in fluorescence intensity or nerve density in the adrenergic nerves of the iris, even when monoamine oxidase was inhibited. 6-Hydroxynoradrenaline administered in vivo, had no effect on the 3H-noradrenaline uptake in the heart. Only when very high concentrations of 6-hydroxynoradrenaline (10 −3 M) were administered in vitro was there a decrease in the 3H-noradrenaline and 3H-dopamine uptake (30–50%) in brain slices of cerebral cortex and striatum and in atria. 6-Hydroxynoradrenaline did not affect retention of 3H-noradrenaline. Inhibition of dopamine-β-hydroxylase did not prevent the decrease of 3H-noradrenaline uptake caused by 6-hydroxydopamine. Present results show that 6-hydroxynoradrenaline has a low affinity for the uptake sites of the catecholamine neuron and is therefore not accumulated within the neuron. It is suggested that this is the reason why 6-hydroxynoradrenaline failed to produce noradrenaline depletion and neuronal degeneration. A conversion of 6-hydroxydopamine. to 6-hydroxynoradrenaline is not a requirement for the production of neuronal degeneration by 6-hydroxydopamine.