Pfeiffer A, Hanack C, Kopp R, Tacke R, Moser U, Mutschler E, Lambrecht G, Herawi M
Medizinische Klinik II, Klinikum Grosshadern, Universität München, F.R.G.
Dig Dis Sci. 1990 Dec;35(12):1468-72. doi: 10.1007/BF01540563.
Five subtypes of muscarinic receptors have been distinguished by pharmacological and molecular biological methods. This report characterizes the muscarinic subtype present in human gastric mucosa by radioligand binding studies. The receptor density was 27 +/- 6 fmol/mg protein and the tritiated ligand N-methylscopolamine had an affinity of (KD) 0.39 +/- 0.08 nM (n = 11). The M1 receptor selective antagonist pirenzepine and the M2 receptor selective ligand AF-DX 116 had low affinities of 148 +/- 32 nM (n = 13) and 4043 +/- 1011 nM (n = 3) KD, respectively. The glandular M3 antagonists hexahydrosiladifenidol and silahexocyclium had high affinities of KD 78 +/- 23 nM (n = 5) and 5.6 +/- 1.8 nM (n = 3). The agonist carbachol interacted with a single low-affinity site and binding was insensitive to modulation by guanine nucleotides. Antagonist and agonist binding studies thus showed an affinity profile typical of M3 receptors of the glandular type.
通过药理学和分子生物学方法已区分出五种毒蕈碱受体亚型。本报告通过放射性配体结合研究对人胃黏膜中存在的毒蕈碱亚型进行了表征。受体密度为27±6 fmol/mg蛋白质，氚化配体N-甲基东莨菪碱的亲和力（KD）为0.39±0.08 nM（n = 11）。M1受体选择性拮抗剂哌仑西平和M2受体选择性配体AF-DX 116的亲和力较低，KD分别为148±32 nM（n = 13）和4043±1011 nM（n = 3）。腺体型M3拮抗剂六甲硅铵和西拉环铵具有较高的亲和力，KD分别为78±23 nM（n = 5）和5.6±1.8 nM（n = 3）。激动剂卡巴胆碱与单个低亲和力位点相互作用，且结合对鸟嘌呤核苷酸的调节不敏感。拮抗剂和激动剂结合研究因此显示出腺体型M3受体典型的亲和力特征。
