Effects of Tianeptine on The Activity of Glutamate Transporter EAAT3 Expressed in Xenopus Oocytes
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Objectives : Tianeptine is an antidepressant that has drawn attention recently. Unlike traditional monoaminergic antidepressants, tianeptine is known to affect glutamate neurotransmission like ketamine. However, there has been paucity of studies investigating the role of tianeptine on glutamate transporters, especially excitatory amino acid transporter type 3 (EAAT3). Methods : After expression of EAAT3 by intracellular injection of EAAT3 mRNA, we investigated the effect of tianeptine on the activity of EAAT3, by measuring membrane current in response to L-glutamate administration using Xenopus oocyte expression system and two-electrode voltage clamps. Results : Tianeptine (1mM for 72h) significantly reduced Vmax (6.9±0.6 vs. 4.8±0.3mC, n=14-22, p<0.05) without changing Km (27.0±7.6 vs. 23.3±4.9mM, n=14-22, p=0.72). Conclusion : When tianeptine was exposed for 72h, it decreased the activity of EAAT3 in a concentration-dependent manner (1-100mM). Our results suggest that tianeptine decreases EAAT3 activity by reducing the available number or turnover rate of EAAT3.
Abstract
Objectives : Tianeptine is an antidepressant that has drawn attention recently. Unlike traditional monoaminergic antidepressants, tianeptine is known to affect glutamate neurotransmission like ketamine. However, there has been paucity of studies investigating the role of tianeptine on glutamate transporters, especially excitatory amino acid transporter type 3 (EAAT3). Methods : After expression of EAAT3 by intracellular injection of EAAT3 mRNA, we investigated the effect of tianeptine on the activity of EAAT3, by measuring membrane current in response to L-glutamate administration using Xenopus oocyte expression system and two-electrode voltage clamps. Results : Tianeptine (1mM for 72h) significantly reduced Vmax (6.9±0.6 vs. 4.8±0.3mC, n=14-22, p<0.05) without changing Km (27.0±7.6 vs. 23.3±4.9mM, n=14-22, p=0.72). Conclusion : When tianeptine was exposed for 72h, it decreased the activity of EAAT3 in a concentration-dependent manner (1-100mM). Our results suggest that tianeptine decreases EAAT3 activity by reducing the available number or turnover rate of EAAT3.
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