Studies on the mechanism of antidepressants using clonal cell lines.

研究慢性抗抑郁药治疗对C6完整培养细胞<bet - >-肾上腺素受体数量及异丙肾上腺素刺激下环amp积累的直接影响。细胞用10^<-5> M的去丙咪嗪（DMI）、丙咪嗪（IMI）或米安色林（MIA）慢性处理5天。用放射性配体^3H-CGP-12177进行结合研究。这些处理没有引起<bet - >-肾上腺素受体数量的减少，也没有改变其亲和力。另一方面，慢性暴露于DMI或MIA（4天）导致异丙肾上腺素诱导的环AMP积累以剂量依赖的方式减少（10^<-7> M -10^<-5> M）。当氟哌啶醇培养细胞时，异丙肾上腺素诱导的环状AMP积累减少仅在10^<-5> M和5 × 10^<-6> M浓度下发现。这表明抗抑郁药（DMI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，抗抑郁药的10^<-6>-10^<-7> M的浓度应用于此类实验，因为我们发现环AMP的反应随10^<-5>-10^<-6> M的变化对抗抑郁药没有特异性。

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.