Studies on the mechanism of antidepressants using clonal cell lines.

使用克隆细胞系研究抗抑郁药的作用机制。

• 批准号: 61570529
• 负责人: HIGUCHI Teruhiko
• 金额: $ 1.41万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570529/
• 关键词: C6 glioma cells; <beta>-adrenoceptor; cyclic AMP; cyclic AMP; パロキセチン結合; 再とり込み機構; 神経系腫瘍細胞; PC-12細胞; 【C_6】細胞; チロシン水酸化酵素活性; 【β_3】レセプター

The direct effects of chronic treatment with the anti-depressants on the number of <bet>-adrenoceptors and the accumulation of cyclic-AMP stimulated with isoproterenol were studied on C6 intact cultured cells. The cells were treated chronically for 5 days with 10^<-5> M decipramine (DMI), imipramine (IMI) or mianserin(MIA). Binding studies were performed with the radioligand ^3H-CGP-12177. These treatment did not induce the decrease in the number of <bet>-adrenoceptors nor the change of affinity. On the other hand, chronic exposure (4 days) to DMI or MIA led to a decrease in isoproterenol-induced accumulation of cyclic AMP in a dose dependent manner (10^<-7> -10^<-5> M). When the cells were cultured with haloperidol, the decrease in isoproterenol-induced accumulation of cyclic AMP was found only in the concentration of 10^<-5> M and 5x10^<-6> M. These result suggest that antidepressants (DMI and MIA) directly act on the secondmessenger system without any change of <bet>-adrenoceptors when these drugs were administered chronically. In addition, the concentration of 10^<-6>-10^<-7> M of antidepressants should be used for these kind of experiments because the change of the response of cyclic AMP with 10^<-5>-10^<-6> M was found to be not specific for antidepressants.

在<bet>C6完整培养细胞上研究了抗抑郁药对肾上腺素能受体数量和异丙肾上腺素刺激的环AMP积累的长期治疗的直接影响。用10 μ M的<-5>去甲丙咪嗪（Decipramine，DECK）、丙咪嗪（Imipramine，IMI）或米安色林（Mianserin，MIA）长期处理细胞5天。用放射性配体^3 H-CGP-12177进行结合研究。这些处理并不引起β-肾上腺素能受体数量的减少<bet>，也不引起亲和力的改变。另一方面，慢性暴露于（4天）异丙肾上腺素或MIA导致异丙肾上腺素诱导的环腺苷酸蓄积以剂量依赖性方式减少（10 μ <-7>M-10 μ <-5>M）。当细胞与氟哌啶醇一起培养时，仅在10 μ M和5 × 10 μ M浓度下发现异丙肾上腺素诱导的环AMP积累减少<-5><-6>。这些结果表明，抗抑郁药（抗抑郁药和MIA）在长期给药时直接作用于第二信使系统，而不改变<bet>肾上腺素受体。此外，由于10 ^<-6>-10 ^<-7>M的cAMP反应的变化对抗抑郁药没有特异性，因此，在这类实验中应使用10^<-5>-10 ^<-6>M的抗抑郁药。

项目成果

渡辺義文: 精神薬療基金年報 第18集. (1987)

Yoshifumi Watanabe：精神药物治疗基金年度报告第 18 卷。（1987 年）

渡辺義文: 精神医学. 29. 1271-1276 (1987)

渡边义文：精神病学。29. 1271-1276 (1987)

樋口輝彦: "神経系培養細胞を用いた抗うつ薬の作用機序に関する研究(第一報)" 昭和62年度厚生省神経疾患研究委託費報告書, (1987)

樋口照彦：“利用培养的神经系统细胞研究抗抑郁药的作用机制（第一次报告）”1985年厚生省神经疾病研究委托基金报告，（1987年）

Yoshifumi Watanabe: "Effects of Chronic Antidepressant Treatment on Serotonin Reuptake Mechanism and Paroxetine Binding Sites" CLINICAL PSYCHIATRY. 29. 1271-1276 (1987)

Yoshifumi Watanabe：“慢性抗抑郁治疗对血清素再摄取机制和帕罗西汀结合位点的影响”临床精神病学。