van Koppen C J, Rodrigues de Miranda J F, Beld A J, Hermanussen M W, Lammers J W, van Ginneken C A
Naunyn Schmiedebergs Arch Pharmacol. 1985 Nov;331(2-3):247-52. doi: 10.1007/BF00634245.
Muscarinic receptors in human tracheal smooth muscle were characterized by radioligand binding and functional studies. Specific [3H]-(-)-quinuclidinylbenzilate ([3H]-(-)-QNB) binding to tracheal smooth muscle membranes was reversible, stereoselective and of high affinity (Kd = 47 +/- 4 pmol/l; RT = 920 +/- 120 fmol/g tissue). Inhibition of specific [3H]-(-)-QNB binding by the M-1 selective antagonist pirenzepine was found to occur at relative high concentrations classifying the muscarinic receptor population as belonging to the M-2 subclass. Inhibition of specific [3H]-(-)-QNB binding by muscarinic agonists revealed the presence of high and low affinity sites in nearly equal proportions. 5'-Guanylylimidodiphosphate converted high affinity sites into low affinity sites although its effect was minimal. Log dose-contraction curves of methacholine had Hill coefficients of 1.10 +/- 0.04 with pD2-values of 6.75 +/- 0.02. Inhibition of specific [3H]-(-)-QNB binding by methacholine, however, was best described by a two binding site model with pKi-values considerably lower. The difference between these affinity values points to the presence of substantial receptor reserve.
通过放射性配体结合和功能研究对人气管平滑肌中的毒蕈碱受体进行了表征。特异性[3H]-（-）-奎宁环基苯甲酸酯（[3H]-（-）-QNB）与气管平滑肌膜的结合是可逆的、立体选择性的且具有高亲和力（Kd = 47±4 pmol/l；RT = 920±120 fmol/g组织）。发现M-1选择性拮抗剂哌仑西平对特异性[3H]-（-）-QNB结合的抑制作用在相对较高浓度下发生，将毒蕈碱受体群体归类为属于M-2亚类。毒蕈碱激动剂对特异性[3H]-（-）-QNB结合的抑制作用显示高亲和力和低亲和力位点的比例几乎相等。5'-鸟苷酰亚胺二磷酸将高亲和力位点转化为低亲和力位点，尽管其作用最小。乙酰甲胆碱的对数剂量-收缩曲线的希尔系数为1.10±0.04，pD2值为6.75±0.02。然而，乙酰甲胆碱对特异性[3H]-（-）-QNB结合的抑制作用最好用具有相当低的pKi值的双结合位点模型来描述。这些亲和力值之间的差异表明存在大量的受体储备。
