Okada F, Horikawa T, Tokumitsu Y, Nomura Y
Health Administration Center, Hokkaido University, Sapporo, Japan.
Neurochem Int. 1994 Jan;24(1):23-7. doi: 10.1016/0197-0186(94)90125-2.
The response of adenylate cyclase to GTP and to dopamine (DA) was investigated in striatal membranes from desipramine (DMI)- or saline-treated rats. DMI (15 mg/kg) or saline was injected i.p. once a day for 3 weeks. In saline-treated control membranes, GTP exerted a biphasic effect on basal and DA-stimulated enzyme activity; peak levels of stimulation by DA plus GTP were observed at 1 microM GTP. On the other hand, peak levels moved to the right in the GTP dose response curve in DMI-treated membranes. Therefore, D2 inhibition might be attenuated, while the D2 specific agonist, PPHT, was not observed to cause inhibition of adenylate cyclase. Furthermore, D1 stimulation of adenylate cyclase via D1 specific agonist SKF was attenuated in DMI-treated membranes. It seems, therefore, that chronic treatment of rat striatum with DMI exerts a dual influence, that is, a lessening of both D1 stimulation and D2 inhibition of adenylate cyclase, and alters specifically the overall process of the adenylate cyclase system.
在经去甲丙咪嗪(DMI)或生理盐水处理的大鼠纹状体膜中,研究了腺苷酸环化酶对鸟苷三磷酸(GTP)和多巴胺(DA)的反应。每天腹腔注射DMI(15毫克/千克)或生理盐水,持续3周。在生理盐水处理的对照膜中,GTP对基础和DA刺激的酶活性产生双相作用;在1微摩尔GTP时观察到DA加GTP刺激的峰值水平。另一方面,在DMI处理的膜中,GTP剂量反应曲线中的峰值水平向右移动。因此,D2抑制作用可能减弱,而D2特异性激动剂PPHT未观察到对腺苷酸环化酶的抑制作用。此外,在DMI处理的膜中,通过D1特异性激动剂SKF对腺苷酸环化酶的D1刺激作用减弱。因此,似乎用DMI对大鼠纹状体进行慢性处理会产生双重影响,即腺苷酸环化酶的D1刺激作用和D2抑制作用均减弱,并特异性地改变腺苷酸环化酶系统的整体过程。