Waelbroeck M, Tastenoy M, Camus J, Christophe J
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
Mol Pharmacol. 1990 Aug;38(2):267-73.
To compare the proportions of four muscarinic receptors in different rat brain regions, we used competition curves with four selective antagonists, at 1-[N-methyl-3H]scopolamine methyl chloride [( 3H]NMS) binding equilibrium and after allowing [3H]NMS dissociation for 35 min. Himbacine and methoctramine were shown to discriminate two muscarinic receptor subtypes having a high affinity for 4-diphenylacetoxy-N-methylpiperidine methiodide and hexahydrosiladifenidol, intermediate affinity for pirenzepine, and low affinity for AF-DX 116. One M4 subtype had a high affinity for himbacine and methoctramine; it was found predominantly in homogenates from rat striatum (46% of total [3H]NMS receptors) and in lower proportion in cortex (33% of [3H]NMS receptors) and hippocampus (16% of [3H]NMS receptors). Its binding properties were identical to those of muscarinic receptors in the neuroblastoma x glioma NG 108-15 hybrid, suggesting that it was encoded by m4 mRNA. The M3 subtype (typically found in rat pancreas, a tissue expressing the m3 mRNA) had a low affinity for himbacine and methoctramine and represented about 10% of all [3H]NMS receptors in rat brain cortex, hippocampus, striatum, and cerebellum. M1 and M2 receptors were identified in rat brain by their high affinity for pirenzepine and AF-DX 116, respectively.
为比较四种毒蕈碱受体在不同大鼠脑区中的比例，我们使用了四种选择性拮抗剂的竞争曲线，分别在1-[N-甲基-3H]东莨菪碱甲基氯（[3H]NMS）结合平衡时以及让[3H]NMS解离35分钟后进行检测。已证实樟柳碱和甲奥克生能区分两种毒蕈碱受体亚型，这两种亚型对4-二苯基乙酰氧基-N-甲基哌啶甲基碘化物和六氢硅二苯醚具有高亲和力，对哌仑西平具有中等亲和力，对AF-DX 116具有低亲和力。一种M4亚型对樟柳碱和甲奥克生具有高亲和力；主要在大鼠纹状体匀浆中发现（占总[3H]NMS受体的46%），在皮层（占[3H]NMS受体的33%）和海马体（占[3H]NMS受体的16%）中比例较低。其结合特性与神经母细胞瘤x胶质瘤NG 108-15杂交细胞中的毒蕈碱受体相同，表明它由m4 mRNA编码。M3亚型（通常在大鼠胰腺中发现，该组织表达m3 mRNA）对樟柳碱和甲奥克生具有低亲和力，约占大鼠脑皮层、海马体、纹状体和小脑中所有[3H]NMS受体的10%。M1和M2受体分别通过对哌仑西平和AF-DX 116的高亲和力在大鼠脑中得以鉴定。
