Hammer R, Giraldo E, Schiavi G B, Monferini E, Ladinsky H
Life Sci. 1986 May 5;38(18):1653-62. doi: 10.1016/0024-3205(86)90409-1.
The heterogeneity of muscarine receptors was examined in two brain regions (cerebral cortex and cerebellum) and in some parasympathetically innervated peripheral tissues (heart, salivary gland and intraorbital lacrimal gland), by in vitro binding techniques. As a tool, we used a new antimuscarinic compound, AF-DX 116 (see text for structural formula and chemical name). In competition experiments against 3H-N-methylscopolamine (3H-NMS) or 3H-pirenzepine (3H-PZ), AF-DX 116 was found to bind with high affinity to muscarine receptors in the heart and cerebellum (KD's approximately equal to 115 nM), with intermediate affinity to M1 receptors in neuronal tissue (KD = 760 nM) and with low affinity to receptors in exocrine glands (KD's approximately equal to 3200 nM). Its receptor interaction was found to be of the simple, competitive type. Thus, AF-DX 116 shows a novel cardioselective profile. On the basis of the results which demonstrate that the muscarine receptors in the heart and exocrine glands are clearly distinct, it is proposed that these receptors may be subclassified as M2 cardiac type and M2 glandular type muscarine receptors.
通过体外结合技术，在两个脑区（大脑皮层和小脑）以及一些受副交感神经支配的外周组织（心脏、唾液腺和眶内泪腺）中检测了毒蕈碱受体的异质性。作为一种工具，我们使用了一种新的抗毒蕈碱化合物AF-DX 116（结构式和化学名称见正文）。在与3H-N-甲基东莨菪碱（3H-NMS）或3H-哌仑西平（3H-PZ）的竞争实验中，发现AF-DX 116与心脏和小脑中的毒蕈碱受体具有高亲和力（KD约等于115 nM），与神经元组织中的M1受体具有中等亲和力（KD = 760 nM），与外分泌腺中的受体具有低亲和力（KD约等于3200 nM）。发现其受体相互作用为简单的竞争类型。因此，AF-DX 116显示出一种新的心脏选择性特征。基于表明心脏和外分泌腺中的毒蕈碱受体明显不同的结果，有人提出这些受体可细分为M2心脏型和M2腺体型毒蕈碱受体。
