Electrophysiological effect of fluoxetine on Xenopus oocytes heterolo-gously expressing human seroto

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:abcprint
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Aim:To investigate the electrophysiological effect of fluoxetine on serotonintransporter.Methods:A heterologous expression system was used to introducehuman serotonin transporter(hSERT)into Xenopus oocytes.A 2-electrode volt-age clamp technique was used to study the pharmacological properties offluoxetine.Results:hSERT-expressing oocytes were perfused with 10 μmol/Lserotonin(5-HT)to induce hSERT-current.The 5-HT-induced hSERT currentswere dose-dependently reversed by fluoxetine.The RC_(50)(concentration thatachieved a 50% reversal)was approximately 3.12 μmol/L.Fluoxetine took moretime to combine with hSERT than 5-HT did,and it was also slow to dissociate fromhSERT.This long-lasting effect of fluoxetine affected normal 5-HT transport.Fluoxetine significantly prolonged the time constant for 5-HT-induced hSERTcurrent.These results might be used to explain the long-lasting anti-anxiety effectof fluoxetine in clinical practice,because it increases the concentration of 5-HT inthe 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 chang-ing the normal dynamics of hSERT. Aim: To investigate the electrophysiological effect of fluoxetine on seroton transransporter. Methods: A heterologous expression system was used to introducehuman serotonin transporter (hSERT) into Xenopus oocytes. A 2-electrode volt-age clamp technique was used to study the pharmacological properties offluoxetine. Results hSERT-expressing oocytes were perfused with 10 μmol / L serotonin (5-HT) to induce hSERT-current. The 5-HT-induced hSERT currentswere dose-dependently reversed phase injection of 50% reversal ) was approximately 3.12 μmol / L.Fluoxetine took moretime to combine with hSERT than 5-HT did, and it was also slow to dissociate fromhSERT.This long-lasting effect of fluoxetine affected normal 5-HT transport. Fluoxetine significantly prolonged the time constant for 5-HT-induced hSERTcurrent.These results might be used to explain the long-lasting anti-anxiety effectof fluoxetine in clinical practice, because it increases the concentration of 5-HT inthe synaptic cleft by its enduring suppression of the function of 5-HT transporters. Confluence: Fluoxetine inhibits 5-HT reuptake by competing with 5-HT and chang-ing the normal dynamics of hSERT.
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