Carrier-mediated Serotonin Release Induced by d-Fenfluramine: Studies with Human Neuroblastoma Cells Transfected with a Rat Serotonin Transporter

Abstract The NMB human neuronal cell line, transfected with a newly prepared plasmid expressing rat serotonin transporter (NMB-rSERT), shows specific [ 3 H]5-HT uptake which is blocked by citalopram and fenfluramine (F) stereoisomers with ic 50 values (1 nM, 0.5 μM (dF) and 5 μM (IF), respectively) which are similar to those found in rat brain synaptosomes. d-Fenfluramine (0.5 and 10 μM) also stimulates tritium release from NMB-rSERT cells preloaded with [ 3 H-]-5-HT. The d-fenfluramine-induced [ 3 H-]5-HT release is blocked by 0.3 μM citalopram and is dependent on the density of SERT expressed per cell, but is not affected by removal of Ca ++ ions from the incubation medium. Manipulation of the Na + gradient across the plasma membrane (replacing 60 mM NaCl with an equimolar concentration of KCl or choline) also induced [ 3 H-]5-HT release from NMB-rSERT cells, which was inhibited by 0.3 μM citalopram. These results, together with the finding that NMB-rSERT cells preloaded with 500 nM unlabelled 5-HT take up [ 3 H-]d-fenfluramine, make NMB-rSERT cells a valuable tool for studying the transporter-mediated exchange release induced by amphetamine derivatives. © 1997 Published by Elsevier Science Ltd.