M. Cinquanta et al., CARRIER-MEDIATED SEROTONIN RELEASE INDUCED BY D-FENFLURAMINE - STUDIES WITH HUMAN NEUROBLASTOMA-CELLS TRANSFECTED WITH A RAT SEROTONIN TRANSPORTER, Neuropharmacology, 36(6), 1997, pp. 803-809
The NMB human neuronal cell line, transfected with a newly prepared pl
asmid expressing rat serotonin transporter (NMB-rSERT), shows specific
[H-3]5-HT uptake which is blocked by citalopram and fenfluramine (F)
stereoisomers with IC50 values (1 nM, 0.5 mu M (dF) and 5 mu M (1F), r
espectively) which are similar to those found in rat brain synaptosome
s. d-Fenfluramine (0.5 and 10 mu M) also stimulates tritium release fr
om NMB-rSERT cells preloaded with [H-3-]- 5-HT. The d-fenfluramine-ind
uced [H-3-]5-HT release is blocked by 0.3 mu M citalopram and is depen
dent on the density of SERT expressed per cell, but is not affected by
removal of Ca++ ions from the incubation medium. Manipulation of the
Nat gradient across the plasma membrane (replacing 60 mM NaCl with an
equimolar concentration of KCl or choline) also induced [H-3-]5-HT rel
ease from NMB-rSERT cells, which was inhibited by 0.3 mu M citalopram.
These results, together with the finding that NMB-rSERT cells preload
ed with 500 nM unlabelled 5-HT take up [H-3-]d-fenfluramine, make NMB-
rSERT cells a valuable tool for studying the transporter-mediated exch
ange release induced by amphetamine derivatives. (C) 1997 Published by
Elsevier Science Ltd.