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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Long-term neuroleptic treatments counteract dopamine D2 agonist inhibition of adenylate cyclase but do not affect pertussis toxin ADP-ribosylation in the rat brain.
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Long-term neuroleptic treatments counteract dopamine D2 agonist inhibition of adenylate cyclase but do not affect pertussis toxin ADP-ribosylation in the rat brain.

机译：长期的抗精神病药物治疗可抵消多巴胺D2激动剂对腺苷酸环化酶的抑制作用，但不会影响大鼠脑中的百日咳毒素ADP-核糖基化。

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摘要

We have investigated the response of adenylate cyclase to GTP and to dopamine (DA) in striatal membranes of rats treated for 3 weeks with chlorpromazine or haloperidol, and further measured the level of Gi (an inhibitory GTP-binding protein) or Go (a similar GTP-binding protein of unknown function) in 3 areas (cerebral cortex, striatum and hippocampus) utilizing pertussis toxin-catalyzed ADP ribosylation. 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. Conversely, dopaminergic inhibitory effects at 10-100 microM GTP were completely attenuated in chlorpromazine or haloperidol-treated membranes. D2 inhibition of adenylate cyclase by the selective D2 agonist PPHT was also attenuated due to these neuroleptic treatments, while an increase in D2 receptor binding was observed. The pertussis toxin ADP-ribosylation of G-proteins (Gi/Go) did not differ significantly in any area.This indicates that long-term neuroleptic treatments increased D2 receptor binding, but attenuated D2 inhibition of adenylate cyclase, and exercised no influence on pertussis toxin ADP-ribosylation.
机译：我们研究了用氯丙嗪或氟哌啶醇处理3周的大鼠的纹状体膜中腺苷酸环化酶对GTP和多巴胺（DA）的反应，并进一步测量了Gi（一种抑制性GTP结合蛋白）或Go（类似利用百日咳毒素催化的ADP核糖基化作用在3个区域（大脑皮层，纹状体和海马体）中功能未知的GTP结合蛋白。在盐水处理过的对照膜中，GTP对基础和DA刺激的酶活性产生双相作用-在1 microM GTP处观察到DA + GTP刺激的峰值水平。相反，在氯丙嗪或氟哌啶醇处理过的膜中，对10-100 microM GTP的多巴胺能抑制作用被完全减弱。由于这些抗精神病药物的治疗，选择性D2激动剂PPHT对腺苷酸环化酶的D2抑制作用也减弱了，同时观察到D2受体结合的增加。百日咳毒素G蛋白（Gi / Go）的ADP-核糖基化在任何区域均无显着差异，这表明长期的抗精神病药物治疗可增加D2受体结合，但减弱D2对腺苷酸环化酶的抑制作用，并且对百日咳没有影响毒素ADP-核糖基化。

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