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 C6 完整培养细胞上研究了抗抑郁药长期治疗对异丙肾上腺素刺激的 β-肾上腺素受体数量和环 AMP 积累的直接影响。用10 -5 M地昔帕明(DMI)、丙咪嗪(IMI)或米安舍林(MIA)长期处理细胞5天。使用放射性配体^3H-CGP-12177 进行结合研究。这些治疗没有引起β-肾上腺素受体数量的减少，也没有引起亲和力的变化。另一方面，长期暴露(4天)DMI或MIA导致异丙肾上腺素诱导的环AMP积累以剂量依赖性方式减少(10^-7-10^-5M)。当用氟哌啶醇培养细胞时，仅在10^-5M和5x10^-6M浓度下发现异丙肾上腺素诱导的环AMP积累减少。这些结果表明抗抑郁药（DMI和MIA） ）直接作用于第二信使系统，当长期服用这些药物时，<bet>-肾上腺素受体不会发生任何变化。此外，此类实验应使用10^<-6>-10^<-7>M浓度的抗抑郁药，因为环AMP的响应随10^<-5>-10^<的变化而变化。 -6> M被发现对于抗抑郁药没有特异性。

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。