Tsukahara T, Hongo K, Kassell N F, Ogawa H
Department of Neurological Surgery, University of Virginia School of Medicine, Charlottesville 22908.
J Cardiovasc Pharmacol. 1989 Jun;13(6):870-8. doi: 10.1097/00005344-198906000-00009.
Pharmacodynamic and quantitative autoradiographic studies were performed to characterize the muscarinic receptors on the endothelium and smooth muscle of the rabbit thoracic aorta. The antagonistic effect of atropine and pirenzepine on the relaxation induced by acetylcholine showed that the relaxation was mediated by muscarinic receptors with pA2 values of 9.4 and 6.6, respectively, suggesting the presence of muscarinic receptors on the endothelium with low affinity for pirenzepine. The quantitative autoradiographic study using [3H]-propylbenzilylcholine mustard (3H-PrBCM) showed that the specific 3H-PrBCM binding was time dependent and saturable. Saturation times of the bindings were not significantly different between the receptors on the endothelium and those on the smooth muscle layer. The density of the receptors was higher in the smooth muscle layer than in the endothelium. The specific [3H]-quinuclidinyl benzilate (3H-QNB) binding was displaced by atropine or pirenzepine dose dependently. IC50 of pirenzepine for the receptors on the endothelium was not significantly different from that for the receptors on the smooth muscle layer. These findings suggest that there is a smaller density of muscarinic receptors on the endothelium than on the smooth muscle layer of the rabbit thoracic aorta. The muscarinic receptors on the endothelium can be subclassified into the same subtype as the receptors on the smooth muscle layer, which have low affinity for pirenzepine.
进行了药效学和定量放射自显影研究，以表征兔胸主动脉内皮和平滑肌上的毒蕈碱受体。阿托品和哌仑西平对乙酰胆碱诱导的舒张作用的拮抗效应表明，该舒张作用由毒蕈碱受体介导，其pA2值分别为9.4和6.6，这表明内皮上存在对哌仑西平亲和力较低的毒蕈碱受体。使用[3H]-丙基苯甲酰胆碱芥子碱（3H-PrBCM）的定量放射自显影研究表明，特异性3H-PrBCM结合具有时间依赖性且可饱和。内皮上的受体和平滑肌层上的受体之间的结合饱和时间没有显著差异。受体密度在平滑肌层中高于在内皮中。特异性[3H]-喹核醇基苯甲酸酯（3H-QNB）结合被阿托品或哌仑西平剂量依赖性取代。哌仑西平对内皮上受体的IC50与对平滑肌层上受体的IC50没有显著差异。这些发现表明，兔胸主动脉内皮上的毒蕈碱受体密度低于平滑肌层。内皮上的毒蕈碱受体可细分为与平滑肌层上的受体相同的亚型，这些受体对哌仑西平具有低亲和力。
