Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

The role of the 5-HT transporter (SERT) in the non-exocytotic drug-induced release was critically re-evaluated in superfused rat brain synaptosomes preloaded with [3H]5-HT. We compared the releasing effect of d-fenfluramine (substrate of the carrier with vesicle-depleting action) with that of RO4-1284 (only vesicle-depleting action). d-Fenfluramine induced a SERT- dependent release of unmetabolized [3H]5-HT either in the absence or presence of pargyline. RO4-1284 induced a rapid release of [3H]5-HIAA in the absence of pargyline and a rapid SERT-independent release of unmetabolized [3H]5-HT in the presence of pargyline. These data indicate that in our conditions: 1) in the absence of a carrier substrate, an increase of cytoplasmic 5-HT is followed by rapid metabolism; 2) the (drug-induced) increase in cytoplasmic 5-HT concentration is per se not sufficent to activate a carrier-mediated 5-HT release, which requires also the presence of a carrier substrate. In this case, 5-HT is transported outside more rapidly than it is deaminated; 3) when metabolism is inhibited, cytoplasmic 5-HT may leave the nerve ending through a SERT-independent route, as previously suggested.

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Presentation Number SAgobbi0727
Keywords: 5-HT transporter, d-fenfluramine, RO4-1284, synaptosomes, 5-HT release