On the nature of the adrenergic neuron extragranular amine binding site

Summary

Rat heart slices were incubated with tritium-labeled norepinephrine (NE) or other related amines, exposed to amphetamine or electric field stimulation, and the tritium efflux measured. Pretreatment with reserpine plus the monoamine oxidase inhibitor, pheniprazine, greatly decreased NE efflux following field stimulation, but markedly enhanced amphetamine-induced NE efflux. Pretreatment with 6-hydroxydopamine abolished this effect of amphetamine. Treatment of slices with guanethidine,α-methylnorepinephrine or amantadine also abolished or greatly diminished the amphetamine effect, while phenoxybenzamine or tetrabenazine were without effect. Although amphetamine also released metaraminol, an amine shown to be granule bound even in reserpine-treated systems, amantadine did not, suggesting that amantadine releases amines specifically from an extragranular neuronal binding site. A comparison of release of various amines by field stimulation (a measure of granule amine) and amantadine (a measure of extragranular amine) indicated that the extragranular binding site prefers amines with a catechol group (NE and dopamine) to those without (octopamine, tyramine) and that the beta hydroxyl group is not a significant factor in binding. The extragranular binding site may normally serve as a link in the intraneuronal catecholamine transport system.