Interaction of fluoxetine with the human placental serotonin transporter
| Autor: | Frederick H. Liebach, Vadivel Ganapathy, D. R. Cool |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Serotonin
medicine.medical_specialty Serotonin uptake Placenta In Vitro Techniques Biochemistry Piperidines Pregnancy Fluoxetine Internal medicine medicine Humans Serotonin transporter Pharmacology Microvilli biology Chemistry Transporter Paroxetine Endocrinology Mechanism of action biology.protein Antidepressant Female Serotonin Antagonists medicine.symptom Carrier Proteins medicine.drug |
| Zdroj: | Biochemical Pharmacology. 40:2161-2167 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/0006-2952(90)90249-k |
| Popis: | The interaction of fluoxetine, a non-tricyclic antidepressant, with the human placental serotonin transporter was investigated by studying its influence on [3H]paroxetine binding to the transporter and on [3H]serotonin uptake via the transporter. These studies were done using brush-border membrane vesicles purified from normal term human placentas. Fluoxetine inhibited binding of paroxetine to the membrane vesicles in a concentration-dependent manner, with a Ki value of 3 nM. Kinetic analysis revealed that the inhibition was competitive because the presence of 10 nM fluoxetine increased the Kd for paroxetine from 72 to 461 pM, but had no effect on the Bmax. Fluoxetine also caused a time-dependent dissociation of paroxetine already bound to the transporter. The dissociation followed first-order kinetics. Uptake of serotonin in these membrane vesicles was also inhibited by fluoxetine. The inhibition was concentration dependent with a Ki value of 66 nM at pH 7.5 and 80 nM at pH 6.5. The effect of fluoxetine on the uptake kinetics was to increase the apparent dissociation constant (Kt) for serotonin without influencing the maximal transport capacity (Vmax). The results demonstrate that fluoxetine is a high-affinity ligand and a potent inhibitor of the serotonin transporter found in the human placental brush-border membrane. |
| Databáze: | OpenAIRE |
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