Roffel A F, Ensing K, in 't Hout W G, de Zeeuw R A, Zaagsma J
Department of Pharmacology and Therapeutics, University of Groningen, A. The Netherlands.
Arch Int Pharmacodyn Ther. 1991 Nov-Dec;314:90-104.
In competition experiments with the tertiary radioligand [3H]dexetimide, classical quaternary muscarinic antagonists like ipratropium bromide and N-methylscopolamine bromide distinguished two muscarinic binding sites in bovine brain (total brain minus cerebellum) membranes, in contrast to their tertiary analogues, atropine and scopolamine, which recognized only one binding site. This binding behavior was found to be almost identical in bovine striatal membranes, both in terms of binding affinities and proportions of high (Q1) and low (Q2) affinity binding sites. Both in total brain and in striatal membranes, the Q1/Q2 binding heterogeneity was independent of pirenzepine binding heterogeneity (M1/M2). In peripheral tissues, the binding properties of quaternary muscarinic antagonists varied. Whereas tertiary as well as quaternary compounds showed only high affinity binding towards muscarinic receptors in bovine atrial and left ventricular membranes, heterogeneous binding behavior was observed with quaternary but not with tertiary antagonists in bovine tracheal smooth muscle membranes. The tissue distribution found in the present study suggests that bovine tracheal smooth muscle contraction studies might shed light on the functional significance of the anomalous binding behavior of quaternary muscarinic antagonists.
在与叔放射性配体[3H]右甲溴苯那敏的竞争实验中，经典的季铵型毒蕈碱拮抗剂如异丙托溴铵和溴化N-甲基东莨菪碱在牛脑（全脑减去小脑）膜中区分出两个毒蕈碱结合位点，这与它们的叔胺类似物阿托品和东莨菪碱不同，后者只识别一个结合位点。在牛纹状体膜中，无论是结合亲和力还是高亲和力（Q1）和低亲和力（Q2）结合位点的比例，这种结合行为几乎是相同的。在全脑和纹状体膜中，Q1/Q2结合异质性均独立于哌仑西平结合异质性（M1/M2）。在周围组织中，季铵型毒蕈碱拮抗剂的结合特性各不相同。叔胺化合物和季铵化合物在牛心房和左心室膜中对毒蕈碱受体均只表现出高亲和力结合，而在牛气管平滑肌膜中，季铵拮抗剂表现出异质性结合行为，叔胺拮抗剂则没有。本研究中发现的组织分布情况表明，牛气管平滑肌收缩研究可能有助于阐明季铵型毒蕈碱拮抗剂异常结合行为的功能意义。
