Open AccessElectrophysiological effect of fluoxetine on Xenopus oocytes heterologously expressing human serotonin transporter 1
Author(s) -
WANG Hongwei,
LI Cizhen,
YANG Zhifang,
ZHENG Yanqian,
ZHANG Ying,
LIU Yuanmou
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00274.x
Subject(s) - fluoxetine , xenopus , serotonin , serotonin transporter , voltage clamp , pharmacology , heterologous expression , electrophysiology , patch clamp , serotonin reuptake inhibitor , transporter , serotonin plasma membrane transport proteins , chemistry , biology , endocrinology , neuroscience , biochemistry , recombinant dna , receptor , gene
Aim: 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 μmol/L serotonin (5‐HT) to induce hSERT‐current. The 5‐HT‐induced hSERT currents were dose‐dependently reversed by fluoxetine. The RC 50 (concentration that achieved a 50% reversal) was approximately 3.12 μmol/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. Conclusion: Fluoxetine inhibits 5‐HT reuptake by competing with 5‐HT and changing the normal dynamics of hSERT.