Ariano M A
Department of Anatomy and Neurobiology, University of Vermont, College of Medicine, Burlington 05405.
Neuroscience. 1989;32(1):203-12. doi: 10.1016/0306-4522(89)90119-x.
The morphochemical disposition of the adenylate cyclase-linked dopamine receptor (D1 type) in the rat striatum has been assessed at various time points after a neurotoxic lesion of the dopaminergic afferent pathway to the caudate nucleus. D1 receptor binding sites in the caudate nucleus were determined by in vitro autoradiography of the substituted benzazepine D1 antagonists, [3H]SCH 23390 or [125I]SCH 23982, and contrasted to the pattern of striatal immunohistochemical reactivity of the second messenger compound, cyclic 3',5'-adenosine monophosphate. The results demonstrate that the specific association of this dopamine receptor type with cyclic 3',5'-adenosine monophosphate-stained neurons is abolished at 7 days following chemical interruption of the nigrostriatal pathway, and the receptor disruption is persistent for durations as long as 20 weeks. This investigation suggests that once the postsynaptic receptor pathology is produced by deafferentation, it does not recover the selective morphochemical relationship normally established with the target cell containing the second messenger. This is in contrast to modest biochemical recuperation in D1 dopamine receptor binding seen using this experimental paradigm. This change in D1 dopamine receptor morphochemistry is discussed in relation to the neurochemical deficits produced by dopaminergic denervation and in Parkinson's disease.
在对尾状核多巴胺能传入通路进行神经毒性损伤后的不同时间点，评估了大鼠纹状体中与腺苷酸环化酶相关的多巴胺受体（D1型）的形态化学分布。通过对取代苯并氮杂卓D1拮抗剂[3H]SCH 23390或[125I]SCH 23982进行体外放射自显影来测定尾状核中的D1受体结合位点，并将其与第二信使化合物环3',5'-腺苷单磷酸的纹状体免疫组化反应模式进行对比。结果表明，在黑质纹状体通路化学中断后7天，这种多巴胺受体类型与环3',5'-腺苷单磷酸染色神经元的特异性关联被消除，并且受体破坏持续长达20周。这项研究表明，一旦去传入导致突触后受体病理改变，它就无法恢复与含有第二信使的靶细胞正常建立的选择性形态化学关系。这与使用该实验范式观察到的D1多巴胺受体结合的适度生化恢复形成对比。本文结合多巴胺能去神经支配和帕金森病产生的神经化学缺陷，讨论了D1多巴胺受体形态化学的这种变化。
