STUDIES ON THE MECHANISM OF ANTIDEPRESSANTS USING CLONAL CELL LINES (II)

利用克隆细胞系研究抗抑郁作用机制（二）

• 批准号: 63570511
• 负责人: HIGUCHI Teruhiko
• 金额: $ 1.28万
• 依托单位: GUNMA UNIVERSITY (1989)Saitama Medical University (1988)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570511/
• 关键词: Desipramine; beta-adrenergic receptors; Toxic effect; Intracellular accumulation; C_6 glioma cells; C_6グリオ-マ細胞; 高速液体クロマトグラフィ-; 高速液体クロマトグフィ-; 抗うつ薬; 神経系培養細胞; βーレセプター; ミアンセリン; ハロペリドール

C_6 gliom cells were cultured in the medium containing desipramine(DMI) or haloperidol(HAL) for 4 days. Not only DMI but also HAL, in a dose of 10 muM, reduced the accumulation of cyclic AMP (cAMP) in the cells stimulated by isoproterenol. 10 muM DMI reduced both total cell protein and ATP level in the cells. Intracellular level of DMI was approximately 50-fold more concentrated than the extracellular level. It is likely that 10 muM of DMI in the medium induce toxic effect on C_6 cells due to the accumulation into the cells. Therefore, to investigate the mechanism of action of DMI using C_6 cells, its concentration in the medium should be less than 1 muM. Chronic exposure of C_6 cells to 0.1-1 muM DMI, in which doses neither total cell protein nor ATP level in the cells was affected, did not decrease cAMP accumulation.

将C_6胶质瘤细胞在含去甲丙咪嗪（DESIPRAMINE，HAL）或氟哌啶醇（HAL）的培养基中培养4天。10 μ M剂量的HAL不仅能减少异丙肾上腺素刺激的细胞中cAMP的积累，而且也能减少cAMP的积累。10 μ M的ATP降低了细胞中的总细胞蛋白和ATP水平。胞内水平的α-淀粉酶浓度比胞外水平高约50倍。10 μ M的β-内酰胺酶在培养液中可能由于蓄积而对C_6细胞产生毒性作用。因此，为了研究C_6细胞的作用机制，其在培养基中的浓度应小于1 μ M。C_6细胞长期暴露于0.1-1 μ M的Na_2SO_4，对细胞内总蛋白和ATP水平均无影响，但不减少cAMP的积累。

项目成果

T.Ebisawa: "Toxic Effect of Desipramine on β-adrenergic receptors in C_6 Glioma Cells" European Journal of Pharmacology.

T. Ebisawa：“地昔帕明对 C_6 胶质瘤细胞中 β-肾上腺素能受体的毒性作用”欧洲药理学杂志。

海老沢尚: "精神薬療基金研究年報・第20集" 財団法人精神神経系薬物治療研究基金, 326 (1989)

Hisashi Ebisawa：“精神药物治疗研究年度报告，第 20 卷”精神神经药物治疗研究基金会，326 (1989)

Takashi Ebisawa: "Toxic effect of desipramine on beta-adrenergic receptors in C_6 glioma cells." European J. Pharmacol.

Takashi Ebisawa：“地昔帕明对 C_6 神经胶质瘤细胞中 β-肾上腺素能受体的毒性作用。”

Takashi Ebisawa: "A study of intracellular concentrations of desipramine and its time course." Ann.Rep.Pharmacopsychiat.Res.Found. 1989, 20:185-190.

Takashi Ebisawa：“地昔帕明细胞内浓度及其时间进程的研究。”

T.Ebisawa: "Toxic Effect of Desipramine on β-adrenergie receptors in C_6 Glicma Cells" European Journal of Pharmacology.

T.Ebisawa：“地昔帕明对 C_6 Glicma 细胞中 β-肾上腺素受体的毒性作用”欧洲药理学杂志。