Electrophysiological effect of fluoxetine on Xenopus oocytes heterologously expressing human serotonin transporter1

• Published in: Acta pharmacologica Sinica Vol. 27; no. 3; pp. 289 - 293
• Main Authors: WANG, Hong‐wei, LI, Ci‐zhen, YANG, Zhi‐fang, ZHENG, Yan‐qian, ZHANG, Ying, LIU, Yuan‐mou
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Asia 01.03.2006
• Subjects: 2‐electrode voltage clamp; fluoxetine; heterologous expression; human serotonin transporter
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1111/j.1745-7254.2006.00274.x

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 RC50 (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.