Electrophysiological effect of fluoxetine on Xenopus oocytes heterologously expressing human serotonin transporter.
OBJECTIVE
To investigate the electrophysiological effect of fluoxetine on serotonin transporter.


METHODS
A heterologous expression system was used to introduce human serotonin transporter (hSERT) into Xenopus oocytes. A 2-electrode voltage clamp technique was used to study the pharmacological properties of fluoxetine.


RESULTS
hSERT-expressing oocytes were perfused with 10 micromol/L serotonin (5-HT) to induce hSERT-current. The 5-HT-induced hSERT currents were dose-dependently reversed by fluoxetine. The RC50 (concentration that achieved a 50% reversal) was approximately 3.12 micromol/L. Fluoxetine took more time to combine with hSERT than 5-HT did, and it was also slow to dissociate from hSERT. This long-lasting effect of fluoxetine affected normal 5-HT transport. Fluoxetine significantly prolonged the time constant for 5-HT-induced hSERT current. These results might be used to explain the long-lasting anti-anxiety effect of fluoxetine in clinical practice, because it increases the concentration of 5-HT in the synaptic cleft by its enduring suppression of the function of 5-HT transporters.


CONCLUSIONS
Fluoxetine inhibits 5-HT reuptake by competing with 5-HT and changing the normal dynamics of hSERT.
Wang
Hong-wei
HW
Department of Physiology, Shanghai Jiaotong University Medical School, Shanghai 200025, China.
Li
Ci-zhen
CZ
Yang
Zhi-fang
ZF
Zheng
Yan-qian
YQ
Zhang
Ying
Y
Liu
Yuan-mou
YM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014982:Xenopus laevis
D005473:Fluoxetine; D012701:Serotonin; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors