Release of norepinephrine from organ-cultured superior cervical ganglia: effects of the norepinephrine uptake inhibitor xylamine.

After preloading with [3H]norepinephrine (NE), organ-cultured superior cervical ganglia released increased amounts of [3H]NE when incubated with depolarizing K+ concentrations, tyramine or amphetamine. K+-induced release was Ca++-dependent, whereas tyramine- and amphetamine-induced release were not. Analysis of the released radioactivity by high-pressure liquid chromatography showed that these releasing stimuli caused primarily an increase in NE release, with little increase in the release of NE metabolites. Incubation with 10 microM xylamine, an irreversible inhibitor of NE uptake, caused a small increase in [3H]NE efflux, but no reduction in the endogenous NE and dopamine levels in superior cervical ganglia. After xylamine treatment, tyramine-induced release was greatly inhibited, whereas release by amphetamine and K+ was not. The neuronal uptake inhibitor desipramine (1 microM), affected K+-, tyramine- and amphetamine-induced release in a manner similar to xylamine. It is concluded that xylamine is a very weak releasing agent in this tissue and that its effects on other release processes are consistent with its action as a NE uptake inhibitor. Amphetamine-induced release appears not to require the NE uptake system for either the uptake of amphetamine, as shown by the accumulation of [3H]amphetamine, or the efflux of NE.