title: Effects of BD1047, a σ1receptor antagonist, on the expression of mTOR, Camk2γ and GSK-3β in fluvoxamine-treated N2a cells.
abstract: Fluvoxamine, a common antidepressant agent, is designed to exert its pharmacological effect by inhibiting synaptic serotonin reuptake. However, increasing evidence has demonstrated that σ1receptors are likely to be involved in the mechanism of action of fluvoxamine. The present study aimed to observe the effects of fluvoxamine on the expression levels of mammalian target of rapamycin (mTOR), Ca2+/calmodulin-dependent protein kinase 2γ (Camk2γ) and glycogen synthase kinase-3β (GSK-3β) in fluvoxamine-treated N2a cells and attempted to elucidate whether σ1receptors mediate the pharmacological effects of fluvoxamine. The N2a cells were randomly divided into three groups (each n=6): DMEM group (D group), 0.5 μmol/l fluvoxamine group (F group) and 0.2 μmol/l BD1047 (a σ1receptor antagonist) + 0.5 μmol/l fluvoxamine group (BF group). Western blotting was used to determine the expression levels of mTOR, Camk2γ and GSK-3β in the cultured N2a cells after two days of incubation. The F group exhibited significant increases in the expression levels of mTOR and Camk2γ and a significant reduction in the expression levels of GSK-3β compared with those in the D group (P<0.01). By contrast, the BF group demonstrated significant reductions in the expression levels of mTOR and Camk2γ and a significant increase in the expression levels of GSK-3β, compared with those in the F group (P<0.01). These results suggest that σ1receptors mediate fluvoxamine-elicited changes in the expression levels of mTOR, Camk2γ and GSK-3β in N2a cells, which indicates that σ1receptors are likely to be involved in the pharmacological effects of fluvoxamine.
authors.affiliation: Department of Anesthesiology, The PLA 102 Hospital, Second Military Medical University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Dong-An
authors.initials: DA
authors.lastname: Su
authors.affiliation: Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Ri-Yue
authors.initials: RY
authors.lastname: Jiang
authors.affiliation: Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Liang-Cai
authors.initials: LC
authors.lastname: Ding
authors.affiliation: Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: DA-Ming
authors.initials: DM
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, The PLA 102 Hospital, Second Military Medical University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: En-Shi
authors.initials: ES
authors.lastname: Yan
authors.affiliation: Department of Anesthesiology, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Zhu
authors.affiliation: Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
keywords: Ca2+/calmodulin-dependent protein kinase 2γ; fluvoxamine; glycogen synthase kinase-3β; mammalian target of rapamycin; σ1 receptor antagonist