De Belleroche J, Kilpatrick I C, Birdsall N J, Hulme E C
Brain Res. 1982 Feb 25;234(2):327-37. doi: 10.1016/0006-8993(82)90873-3.
Levels of muscarinic receptors were measured in the nucleus accumbens of rat following 0.8 microgram 6-hydroxydopamine or vehicle injections (0.2 microliter into the ventral tegmental area to investigate whether the dopaminergic terminals destroyed by this procedure bear muscarinic receptors. Dopamine levels in the nucleus accumbens ipsilateral to the injection of 6-hydroxydopamine were substantially reduced by 83% as compared to the unlesioned side after 7 days. Significant decreases in the specific binding of [3H]N-methylscopolamine of 9 and 15% were also seen in the nucleus accumbens ipsilateral to the lesion after 7 and 14 days respectively. The class of muscarinic receptor depleted by the lesion was further investigated using [3H]oxotremorine-M to label the 'super high' affinity binding sites. The percentage occupancy of total muscarinic receptors by [3H]oxotremorine-M was significantly decreased by lesion e.g. 23% after 7 days indicting a selective loss of 'super high' affinity binding sites. The lesion caused no change in the affinity constant for the muscarinic antagonist, propylbenzilylcholine. Studies of the binding of the agonist carbachol and oxotremorine-M by competition with [3H] propylbenzilylcholine showed little change in the concentrations or affinity constants of the 'high' and 'low' affinity binding sites with the 6-hydroxydopamine lesion.
在大鼠伏隔核中测量毒蕈碱受体水平，此前分别注射0.8微克6-羟基多巴胺或赋形剂（0.2微升注入腹侧被盖区），以研究经此操作破坏的多巴胺能终末是否带有毒蕈碱受体。与未损伤侧相比，注射6-羟基多巴胺7天后，注射侧伏隔核中的多巴胺水平大幅降低了83%。在损伤侧伏隔核中，分别在7天和14天后，[3H]N-甲基东莨菪碱的特异性结合也分别显著降低了9%和15%。使用[3H]氧震颤素-M标记“超高”亲和力结合位点，进一步研究了损伤导致减少的毒蕈碱受体类别。损伤使[3H]氧震颤素-M对总毒蕈碱受体的占有率显著降低，例如7天后降低了23%，表明“超高”亲和力结合位点选择性丧失。损伤对毒蕈碱拮抗剂丙基苯甲酰胆碱的亲和力常数没有影响。通过与[3H]丙基苯甲酰胆碱竞争，研究激动剂卡巴胆碱和氧震颤素-M的结合情况，结果显示，6-羟基多巴胺损伤后，“高”亲和力和“低”亲和力结合位点的浓度或亲和力常数变化不大。
