Tonnaer J A, Ernste B H, Wester J, Kelder K
Scientific Development Group, Organon International B.V., Oss, The Netherlands.
J Chem Neuroanat. 1988 Mar-Apr;1(2):95-110.
Employing [3H]hemicholinium-3 ([3H]HC), [3H]pirenzepine([3H]PZ) and [3H]quinuclidinyl benzilate ([3H]QNB), autoradiographic binding studies were performed to identify and quantitate the localization of high-affinity choline carriers, M1-subtype of muscarinic binding sites and a mixed population of M1- and M2-subtypes of muscarinic binding sites, respectively, in 38 anatomically defined areas of rat brain. Labelling of adjacent brain sections with [3H]HC, [3H]PZ and [3H]QNB revealed different topographical binding patterns. [3H]HC binding, which is supposed to reflect cholinergic innervation, was dense in the nucleus accumbens, olfactory tubercle, caudate putamen, basolateral amygdaloid nucleus and the interpeduncular nucleus. Moderate but heterogeneous binding was found in thalamic, hypothalamic, hippocampal and cortical areas. Maximal [3H]PZ binding was observed in the nucleus accumbens, olfactory tubercle and in discrete substructures of the hippocampus, e.g. CA1 and dentate gyrus. Binding to other hippocampal and cortical areas was intermediate, whilst minor binding was found in thalamic, hypothalamic and brain stem areas. The binding of [3H]QNB was more evenly distributed over the brain as compared to that of [3H]PZ. [3H]QNB clearly exceeded the binding of [3H]PZ in the thalamus, hypothalamus and brain stem. A relationship was found between the topography patterns of the [3H]PZ and [3H]QNB binding sites. However, some brain areas showed preference for one of the two ligands, pointing to a distinct localization of M1- and M2-subtypes of muscarinic binding sites. Although M1 sites appeared to predominate in the basal ganglia, hippocampus and cortex, some heterogeneity was observed indicative of the minor occurrence of M2 sites within these structures. There was no relationship between the density of the presumed cholinergic innervation and the binding capacity of either of the muscarinic sites in the various brain areas. However, a relationship was found between M2-selectivity and [3H]HC binding, pointing to a possible presynaptic localization of the M2-sites. In addition, it is suggested that distinct cholinergic cell groups might project their fibres to brain areas containing particular subsets of postsynaptic muscarinic binding sites.
运用[3H]半胆碱-3（[3H]HC）、[3H]哌仑西平（[3H]PZ）和[3H]喹核酯（[3H]QNB）进行放射自显影结合研究，以分别鉴定和定量大鼠脑38个解剖学定义区域中高亲和力胆碱载体、M1型毒蕈碱结合位点以及M1和M2混合型毒蕈碱结合位点的定位。用[3H]HC、[3H]PZ和[3H]QNB对相邻脑切片进行标记，显示出不同的拓扑结合模式。[3H]HC结合被认为反映胆碱能神经支配，在伏隔核、嗅结节、尾状壳核、基底外侧杏仁核和脚间核中密集。在丘脑、下丘脑、海马和皮质区域发现中等但不均匀的结合。在伏隔核、嗅结节和海马的离散亚结构（如CA1和齿状回）中观察到最大的[3H]PZ结合。与其他海马和皮质区域的结合为中等程度，而在丘脑、下丘脑和脑干区域发现少量结合。与[3H]PZ相比，[3H]QNB的结合在脑中分布更均匀。在丘脑、下丘脑和脑干中，[3H]QNB的结合明显超过[3H]PZ。发现了[3H]PZ和[3H]QNB结合位点的拓扑模式之间的关系。然而，一些脑区对两种配体之一表现出偏好，表明M1和M2型毒蕈碱结合位点的独特定位。尽管M1位点似乎在基底神经节、海马和皮质中占主导地位，但观察到一些异质性，表明这些结构中存在少量M2位点。在不同脑区中，假定的胆碱能神经支配密度与任何一种毒蕈碱位点的结合能力之间没有关系。然而，发现M2选择性与[3H]HC结合之间存在关系，表明M2位点可能位于突触前。此外，有人提出，不同的胆碱能细胞群可能将其纤维投射到含有特定突触后毒蕈碱结合位点子集的脑区。
