Marin C, Parashos S A, Chase T N
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD.
Eur J Pharmacol. 1991 Mar 19;195(1):19-25. doi: 10.1016/0014-2999(91)90377-3.
The effect of Gi protein modification produced by intrastriatal pertussis toxin injection on dopamine (DA)-mediated behaviors was studied. Administration of the selective D2 agonist quinpirole induced ipsilateral rotation but the selective D1 agonist SKF 38393 did not. However, SKF 38393 was able to increase the rotation induced by quinpirole. The selective D2 antagonist raclopride and the selective D1 antagonist SCH 23390 both blocked the effect of quinpirole. Striatal levels of cAMP were measured in both intact and pertussis toxin injected striatum. SKF 38393 induced a significant increase in cAMP, but quinpirole had no effect. When both drugs were administered together, quinpirole attenuated the SKF 38393-induced increase in cAMP levels. Moreover, quinpirole-induced attenuation of SKF 38393 effect was greater in intact striatum. In pertussis toxin-injected striatum, quinpirole only attenuated SKF 38393-induced increase of cAMP to control levels. This imbalance between intact and injected striatum might be the cause of the rotation in pertussis toxin-injected rats suggesting an important role for G proteins in DA receptor interactions.
研究了纹状体内注射百日咳毒素所产生的Gi蛋白修饰对多巴胺（DA）介导行为的影响。给予选择性D2激动剂喹吡罗可诱导同侧旋转，但选择性D1激动剂SKF 38393则不能。然而，SKF 38393能够增加喹吡罗诱导的旋转。选择性D2拮抗剂雷氯必利和选择性D1拮抗剂SCH 23390均能阻断喹吡罗的作用。在完整和注射了百日咳毒素的纹状体中均测量了cAMP水平。SKF 38393可诱导cAMP显著增加，但喹吡罗无此作用。当两种药物一起给药时，喹吡罗减弱了SKF 38393诱导的cAMP水平升高。此外，喹吡罗对SKF 38393作用的减弱在完整纹状体中更明显。在注射了百日咳毒素的纹状体中，喹吡罗仅将SKF 38393诱导的cAMP升高减弱至对照水平。完整纹状体和注射纹状体之间的这种失衡可能是注射百日咳毒素大鼠发生旋转的原因，提示G蛋白在DA受体相互作用中起重要作用。
