Distinct primary structures, ligand‐binding properties and tissue‐specific expression of four human muscarinic acetylcholine receptors.
Distinct primary structures, ligand‐binding properties and tissue‐specific expression of four human muscarinic acetylcholine receptors.
复制标题
四种人毒蕈碱乙酰胆碱受体的独特一级结构、配体结合特性和组织特异性表达。
作者：
Peralta Eg;A. Ashkenazi;J. Winslow;Douglas H. Smith;J. Ramachandran;D. Capon
为了研究毒蕈碱胆碱能功能多样性的分子基础，我们分离了编码人类M1和M2毒蕈碱受体（mAChR）的基因以及两种以前未发现的mAChR亚型，命名为HM 3和HM 4。每个亚型的氨基酸序列反映了由7个高度保守的跨膜区段和每个亚型特有的大的细胞内区域组成的结构，其可以分别构成配体结合和效应物偶联结构域。在通过转染哺乳动物细胞产生的单个mAChR亚型中检测到对毒蕈碱配体的亲和力的显著差异。每种亚型对激动剂都表现出多种亲和力状态;亚型之间亲和力和这些位点比例的差异表明mAChR亚型与细胞效应器偶联装置差异相互作用的能力。在心脏、胰腺和神经元细胞系中观察到亚型特异性mRNA表达，表明mAChR基因表达的调节有助于胆碱能活性的分化。
To investigate the molecular basis for the diversity in muscarinic cholinergic function, we have isolated the genes encoding the human M1 and M2 muscarinic receptors (mAChR) as well as two previously undiscovered mAChR subtypes, designated HM3 and HM4. The amino acid sequence of each subtype reflects a structure consisting of seven, highly conserved transmembrane segments and a large intracellular region unique to each subtype, which may constitute the ligand‐binding and effector‐coupling domains respectively. Significant differences in affinity for muscarinic ligands were detected in individual mAChR subtypes produced by transfection of mammalian cells. Each subtype exhibited multiple affinity states for agonists; differences among subtypes in the affinities and proportions of such sites suggest the capacity of mAChR subtypes to interact differentially with the cellular effector‐coupling apparatus. Subtype‐specific mRNA expression was observed in the heart, pancreas and a neuronal cell line, indicating that the regulation of mAChR gene expression contributes to the differentiation of cholinergic activity.