Dadi H K, Batteiger D, Keen M, Morris R J
J Neurochem. 1986 Dec;47(6):1700-5. doi: 10.1111/j.1471-4159.1986.tb13077.x.
The muscarinic receptor for acetylcholine shows a diversity in ligand binding properties and effector mechanisms which have suggested the existence of two subtypes (M1 and M2), to which the selective antagonist pirenzepine binds with markedly different affinities. The receptor from rat brain, covalently labelled with the alkylating antagonist tritiated propylbenzilylcholine mustard, displays a structural microheterogeneity on electrophoresis, covering the region of apparent molecular weight 66,000-76,000, with dominant components at 68,000 and 73,000. Selective inhibition by pirenzepine of labelling of the M1 receptor with tritiated mustard has been analysed on fluorographs of sodium dodecyl sulphate-polyacrylamide gels and shown to cause a uniform reduction in radioactive labelling of the broad receptor peak, rather than selectively inhibiting either the high- or low-molecular-weight regions of the band. It is further shown that although this receptor microheterogeneity is found for each of four brain regions studied, it is not found for the heart receptor, which gives a discrete labelled band of apparent molecular weight 72,000. It is therefore suggested that the structural microheterogeneity is the result of tissue-specific, posttranslational modification of the molecule, such as glycosylation, and is not directly related to the functional diversity of the receptor.
乙酰胆碱的毒蕈碱受体在配体结合特性和效应器机制方面表现出多样性，这提示存在两种亚型（M1和M2），选择性拮抗剂哌仑西平与它们的结合亲和力明显不同。用放射性标记的烷基化拮抗剂氚代丙基苯甲酰胆碱芥子气对大鼠脑受体进行共价标记后，在电泳中显示出结构微不均一性，表观分子量范围为66,000 - 76,000，主要成分在68,000和73,000处。在十二烷基硫酸钠 - 聚丙烯酰胺凝胶的荧光照片上分析了哌仑西平对氚代芥子气标记M1受体的选择性抑制作用，结果表明它会使宽受体峰的放射性标记均匀降低，而不是选择性地抑制条带的高分子量或低分子量区域。进一步表明，尽管在所研究的四个脑区中的每一个都发现了这种受体微不均一性，但在心脏受体中未发现，心脏受体给出一条表观分子量为72,000的离散标记条带。因此，有人提出结构微不均一性是该分子组织特异性翻译后修饰（如糖基化）的结果，与受体的功能多样性没有直接关系。
