Groppetti A, Flauto C, Parati E, Vescovi A, Rusconi L, Parenti M
J Neural Transm Suppl. 1986;22:33-45.
Unilateral lesions of the nigro-striatal dopamine (DA) pathway induced contralateral rotations to apomorphine, increased (3H)-spiroperidol binding and enhanced the sensitivity of striatal adenylate cyclase to DA stimulation. Prolonged L-dopa administration counteracted the increased density of (3H)-spiroperidol binding sites but further enhanced the hypersensitivity of adenylate cyclase to DA and decreased the inhibitory effect of opiates on this enzyme. The apomorphine-induced contralateral rotations were also strongly potentiated. On the contrary the binding of (3H)-SCH-23390 was affected neither by DA nerve degeneration nor by chronic L-dopa treatment. These results suggest that DA-D1 and DA-D2 receptors are differently affected by prolonged L-dopa treatment. The biochemical changes of DA-D1 receptors associated with adenylate cyclase seem to be correlated with the enhanced behavioural responses to apomorphine and could be a consequence of a decreased opiate inhibitory tone on the enzyme. The increased supersensitivity of the DA-D1 receptors may play a role in the clinical changes seen in parkinsonian patients following chronic use of L-dopa.
黑质 - 纹状体多巴胺（DA）通路的单侧损伤导致对阿扑吗啡的对侧旋转，增加了（3H）-螺哌啶醇结合，并增强了纹状体腺苷酸环化酶对DA刺激的敏感性。长期给予左旋多巴可抵消（3H）-螺哌啶醇结合位点密度的增加，但进一步增强了腺苷酸环化酶对DA的超敏反应，并降低了阿片类药物对该酶的抑制作用。阿扑吗啡诱导的对侧旋转也被强烈增强。相反，（3H）-SCH-23390的结合既不受DA神经变性的影响，也不受慢性左旋多巴治疗的影响。这些结果表明，长期左旋多巴治疗对DA-D1和DA-D2受体的影响不同。与腺苷酸环化酶相关的DA-D1受体的生化变化似乎与对阿扑吗啡的行为反应增强有关，并且可能是该酶上阿片类药物抑制作用降低的结果。DA-D1受体超敏反应的增加可能在帕金森病患者长期使用左旋多巴后出现的临床变化中起作用。
