Fornaretto M G, Caccia C, Caron M G, Fariello R G
Department of Neurobiology, Farmitalia Carlo Erba-Erbamont Group, Nerviano, Milan, Italy.
Mol Chem Neuropathol. 1993 May-Jun;19(1-2):147-62. doi: 10.1007/BF03160175.
The physiological effects of dopamine (DA) are mediated by several distinct receptor subtypes. The effects of unilateral nigral 6-hydroxydopamine (6-OHDA) lesions on DA receptors were investigated by receptor autoradiography using the D1 selective ligand [3H]SCH 23390 as well as the D2 ligand [3H]spiroperidol. mRNA distribution was studied by in situ hybridization. Lesioned rats were sacrificed at different time intervals. Receptor binding studies were performed on tissue sections using selective ligands. [35S]UTP labeled RNA probes were prepared from the different cDNA (D1, D2, D3) and used for in situ hybridization. A specific loss of receptor binding sites and mRNA hybridization was found in the lesioned substantia nigra pars compacta (SNc) at all times examined. Receptor binding studies revealed a different time-dependent increase in both D1 and D2 receptors. In situ hybridization showed that only D2 receptor mRNA increased in the caudate-putamen (CPu) of the lesioned side 15 d after 6-OHDA. No changes were observed in D1 and D3 receptor mRNA during the entire time-course.
多巴胺（DA）的生理效应由几种不同的受体亚型介导。采用D1选择性配体[3H]SCH 23390以及D2配体[3H]螺哌啶醇，通过受体放射自显影术研究了单侧黑质6-羟基多巴胺（6-OHDA）损伤对DA受体的影响。通过原位杂交研究mRNA分布。在不同时间间隔处死损伤大鼠。使用选择性配体对组织切片进行受体结合研究。从不同的cDNA（D1、D2、D3）制备[35S]UTP标记的RNA探针，并用于原位杂交。在所检查的所有时间点，均发现损伤的黑质致密部（SNc）中受体结合位点和mRNA杂交出现特异性缺失。受体结合研究显示，D1和D2受体均呈现出不同的时间依赖性增加。原位杂交显示，6-OHDA处理后15天，损伤侧尾状核-壳核（CPu）中仅D2受体mRNA增加。在整个时间进程中，未观察到D1和D3受体mRNA的变化。
