Evidence for the outward transport of norepinephrine in synaptic vesicles attached to the plasma membrane

In a low-sodium, choline⁺ (Ch⁺) medium, rat heart slices, that were labelled in vivo with [³H]norepinephrine, exhibited a delayed, Ca²⁺-dependent release of radioactivity, these radioactive compounds consisted of both amines and deaminated metabolites. The Ca²⁺-dependent release of radioactivity was largely blocked by cocaine suggesting that the release may represent an outward transport of [³H]amines. Reserpine, which is known to inhibit binding of norepinephrine to synaptic vesicles, stimulated the release of deaminated metabolites and some amines from the slices. Cocaine increased the release of [³H]amines in monoamine oxidase inhibited, reserpinized slices in the control medium. When Ch⁺ -Ca²⁺ and reserpine stimulation were combined, the effects of Ch ⁺ -Ca²⁺ predominated. These effects were blocked by cocaine, which then permitted the response to reserpine to become established. The conclusion derived from the above experiments is that norepinephrine coming from synaptic vesicles brought in close proximity to the plasma membrane by a Ca²⁺-dependent system can be transported outwardly to the extraneuronal space by a cocaine-sensitive mechanism.