Walaas S I, Sedvall G, Greengard P
Laboratory of Molecular and Cellular Neurosciences, Rockefeller University, New York, NY 10021.
Neuroscience. 1989;29(1):9-19. doi: 10.1016/0306-4522(89)90328-x.
Dopamine, acting through dopamine D1 receptors and cyclic AMP-dependent protein kinase, has been found to increase the state of phosphorylation of the synaptic vesicle-associated phosphoproteins synapsin I and protein III in slices of rat neostriatum and substantia nigra. In the neostriatum, the effect of dopamine was mimicked by SKF 38393, a D2 receptor agonist, and was abolished by preincubation of the slices with fluphenazine or SCH 23390, antipsychotic drugs which are potent D1 receptor antagonists, but not by the D2 receptor antagonists l-sulpiride or spiroperidol. The maximal effect of dopamine in the neostriatum represented approximately 30-35% of the maximal effect induced by 8-bromo cyclic AMP, suggesting that a similar fraction of nerve terminals in the neostriatum may express the dopamine D1 receptor. Evidence for a small population of beta-adrenergic receptors regulating nerve terminal protein phosphorylation in the neostriatum, distinct from the D1 dopamine receptors, was also obtained. In the substantia nigra, the effect of dopamine also appeared to be mediated through a D1 dopamine receptor, since it was abolished by fluphenazine and SCH 23390. The maximal effect of dopamine in the substantia nigra represented approximately two-thirds of the effect induced by 8-bromo cyclic AMP, suggesting that a similar fraction of nerve terminals in the substantia nigra may express the dopamine D1 receptor. The ability of dopamine D1 receptor activation to stimulate both synapsin I and protein III phosphorylation and GABA release in both the neostriatum and substantia nigra may be causally linked.
已发现多巴胺通过多巴胺D1受体和环磷酸腺苷依赖性蛋白激酶发挥作用，可增加大鼠新纹状体和黑质切片中与突触小泡相关的磷蛋白突触素I和蛋白III的磷酸化状态。在新纹状体中，D2受体激动剂SKF 38393可模拟多巴胺的作用，而将切片与氟奋乃静或SCH 23390（强效D1受体拮抗剂类抗精神病药物）预孵育可消除该作用，但D2受体拮抗剂左旋舒必利或螺哌啶醇则无此作用。多巴胺在新纹状体中的最大作用约占8-溴环磷酸腺苷诱导的最大作用的30%-35%，这表明新纹状体中可能有相似比例的神经末梢表达多巴胺D1受体。还获得了证据，表明新纹状体中存在一小部分调节神经末梢蛋白磷酸化的β-肾上腺素能受体，与D1多巴胺受体不同。在黑质中，多巴胺的作用似乎也通过D1多巴胺受体介导，因为它可被氟奋乃静和SCH 23390消除。多巴胺在黑质中的最大作用约占8-溴环磷酸腺苷诱导作用的三分之二，这表明黑质中可能有相似比例的神经末梢表达多巴胺D1受体。多巴胺D1受体激活在新纹状体和黑质中刺激突触素I和蛋白III磷酸化以及γ-氨基丁酸释放的能力可能存在因果联系。
