On the Relative Importance of Extra‐Neuronal Uptake of Noradrenaline Released by Nerve Stimulation in the Rabbit Heart

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Abstract
Drugs known to inhibit the extra‐neuronal uptake of noradrenaline were given to the sympathetically stimulated, perfused rabbit heart, and the subsequent change in the overflow of transmitter was studied. Normethanephrine (10‐5M) increased the outflow of noradrenaline on nerve stimulation by about 25%, while lower doses were ineffectual. However, in the dose mentioned, the drug did not potentiate the earlier reported increase in overflow caused by desmethylimipramine (5.5 × 10‐7M). On nerve stimulation, intact noradrenaline made up 83% of the increase in radioactivity in the perfusate before, and 94% after, inhibition of the extra‐neuronal uptake of noradrenaline. It is concluded that extraneuronal uptake of noradrenaline, released by sympathetic nerve stimulation, plays a small but significant role in the inactivation of the transmitter from the neuro‐effector junctions. The findings are discussed with regard to earlier observations where phenoxybenzamine, another potent inhibitor of extra‐neuronal uptake, was found to increase the overflow of transmitter on nerve stimulation more than could he expected from its uptake‐inhibiting properties alone.