Studies on the mechanism of antidepressants using clonal cell lines.

在C6完整培养细胞上，研究了慢性抗抑郁药物对肾上腺素能受体数目和异丙肾上腺素刺激的环磷酸腺苷(CAMP)积聚的直接影响。用去甲氧麻黄碱(DMI)、丙咪嗪(IMI)或米安色林(MIA)慢性处理细胞5d。用放射性配基~3H-CGp-12177进行结合研究。这些治疗没有引起肾上腺素受体数目的减少，也没有引起亲和力的改变。另一方面，慢性暴露于DMI或MIA(4天)后，异丙肾上腺素诱导的环磷酸腺苷(CAMP)累积减少，且呈剂量依赖关系(10^&lt；-7&gt；-10^&lt；-5&gt；M)。当细胞与氟哌啶醇共同培养时，只有在10×10~(-5)~(-6)M和5×10~(-6)~(-6)M时，异丙肾上腺素引起的cAMP积聚减少。这些结果表明，长期给药时，抗抑郁药(DMI和MIA)直接作用于第二信使系统，而不改变肾上腺素受体。此外，由于环状AMP对10^&lt；-5&gt；-10^&lt；-6&gt；M的反应变化不是抗抑郁药所特有的，因此在此类实验中应使用10^&lt；-6&gt；-7&gt；M的浓度。

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.