Cortés R, Probst A, Palacios J M
Neuroscience. 1987 Jan;20(1):65-107. doi: 10.1016/0306-4522(87)90006-6.
The distribution of muscarinic cholinergic receptors in the human forebrain and cerebellum was studied in detail by quantitative autoradiography using N-[3H]methylscopolamine as a ligand. Only postmortem tissue from patients free of neurological diseases was used in this study. The highest densities of muscarinic cholinergic receptors were found in the striatum, olfactory tubercle and tuberal nuclei of the hypothalamus. Intermediate to high densities were observed in the amygdala, hippocampal formation and cerebral cortex. In the thalamus muscarinic cholinergic receptors were heterogeneously distributed, with densities ranging from very low to intermediate or high. N-[3H]Methylscopolamine binding was low in the hypothalamus, globus pallidus and basal forebrain nuclei, and very low in the cerebellum and white matter tracts. The localization of the putative muscarinic cholinergic receptors subtypes M1 and M2 was analysed in parallel using carbachol and pirenzepine at a single concentration to partially inhibit N-[3H]methylscopolamine binding. Mixed populations of both subtypes were found in all regions. M1 sites were largely predominant in the basal ganglia, amygdala and hippocampus, and constituted the majority of muscarinic cholinergic receptors in the cerebral cortex. M2 sites were preferentially localized in the diencephalon, basal forebrain and cerebellum. In some areas such as the striatum and substantia innominata there was a tendency to lower densities of muscarinic cholinergic receptors with increasing age. In general, we observed a slight decrease in M2 sites in elderly cases. Muscarinic cholinergic receptor concentrations seemed to be reduced following longer postmortem periods. The distribution of acetylcholinesterase was also studied using histochemical methods, and compared with the localization of muscarinic cholinergic receptors and other cholinergic markers. The correlation between the presence of muscarinic cholinergic receptors and the involvement of cholinergic mechanisms in the function of specific brain areas is discussed. Their implication in neurological diseases is also reviewed.
采用N-[3H]甲基东莨菪碱作为配体，通过定量放射自显影技术对人前脑和小脑中毒蕈碱型胆碱能受体的分布进行了详细研究。本研究仅使用了无神经疾病患者的尸检组织。毒蕈碱型胆碱能受体密度最高的部位是纹状体、嗅结节和下丘脑的结节核。杏仁核、海马结构和大脑皮质观察到中等至高的密度。丘脑中毒蕈碱型胆碱能受体分布不均，密度范围从极低到中等或高。N-[3H]甲基东莨菪碱在下丘脑、苍白球和基底前脑核中的结合较低，在小脑和白质束中非常低。使用单一浓度的卡巴胆碱和哌仑西平平行分析假定的毒蕈碱型胆碱能受体亚型M1和M2的定位，以部分抑制N-[3H]甲基东莨菪碱的结合。在所有区域均发现两种亚型的混合群体。M1位点在基底神经节、杏仁核和海马中占主导地位，并且构成了大脑皮质中毒蕈碱型胆碱能受体的大部分。M2位点优先定位于间脑、基底前脑和小脑。在某些区域，如纹状体和无名质，随着年龄的增长，毒蕈碱型胆碱能受体密度有降低的趋势。总体而言，我们观察到老年病例中M2位点略有减少。毒蕈碱型胆碱能受体浓度似乎在较长的死后时间后降低。还使用组织化学方法研究了乙酰胆碱酯酶的分布，并与毒蕈碱型胆碱能受体和其他胆碱能标记物的定位进行了比较。讨论了毒蕈碱型胆碱能受体的存在与特定脑区功能中胆碱能机制参与之间的相关性。还综述了它们在神经疾病中的意义。
