Efflux of 5-hydroxytryptamine from synaptosomes of rat cerebral cortex.

The efflux of 3H-5-HT from a crude synaptosome preparation of the cerebral cortex of reserpinized rats was examined. The synaptosomes were loaded with 3H-5-HT by pre-incubation of the homogenate in presence of pargyline and desipramine in order to inhibit deamination of 5-HT and uptake into noradrenergic neurons. The synaptosomes were collected by centrifugation, washed and resuspended in 0.25 M sucrose. No spontaneous efflux of 5-HT was detectable at 0 degrees C but marked efflux was observed at 27 degrees C and 37 degrees C. 4-Chloroamphetamine, low external Na+ concentration, ouabain and the depolarizing agent veratridine markedly accelerated the initial (5 min) efflux. Inhibitors of the neuronal 5-HT uptake, e.g. chlorimipramine, H 102/09 and A 23189, antagonized the 5-HT efflux evoked by these means, whereas desipramine, which is a poor inhibitor of the 5-HT uptake, had only slight effect on the 5-HT efflux. It is suggested that 5-HT can be actively transported out from the synaptosomes by the reversed 5-HT uptake mechanism.