Sim M K, Manjeet S
Department of Pharmacology, Faculty of Medicine, National University of Singapore.
Clin Exp Hypertens. 1993 Mar;15(2):409-21. doi: 10.3109/10641969309032943.
The muscarinic receptors in the aorta of the normo- and hypertensive rats were characterised with tritiated acetylcholine (3H-ACh) and various muscarinic receptor antagonists. The binding of 3H-ACh to the endothelial membranes of the normotensive Wistar Kyoto rats (WKY) and the spontaneously hypertensive rats (SHR) was displaceable by nanomolar range of scopolamine but only by micromolar range of atropine and homatropine. The reverse was observed with the muscle binding sites, i.e. the 3H-ACh was displaceable by nanomolar range of atropine and homatropine but only by micromolar range of scopolamine. Pirenzepine and 4-diphenyl-acetoxy-N-methyl-piperidine metobromide (4-DAMP) displaced the binding of 3H-ACh from both tissues in the nano to micromolar range, with the displacement from the endothelial binding sites occurring at lower concentration range of the ligands. The apparent IC50 values of both compounds for the smooth muscle were 9 and 16 times greater than those for the endothelial binding sites respectively. When saturated with guanylyl-imididiphosphate (GppNHp), conversion of high to low-affinity binding site occurred in both tissues of the WKY but only in the smooth muscle of the SHR. GppNHp had no apparent effect on the binding of 3H-ACh to the endothelial binding sites confirming that the high-affinity site for 3H-ACh was missing in the endothelium of the SHR.
用氚标记的乙酰胆碱（3H-ACh）和各种毒蕈碱受体拮抗剂对正常血压和高血压大鼠主动脉中的毒蕈碱受体进行了表征。3H-ACh与正常血压的Wistar Kyoto大鼠（WKY）和自发性高血压大鼠（SHR）内皮细胞膜的结合可被纳摩尔范围的东莨菪碱取代，但仅能被微摩尔范围的阿托品和后马托品取代。在肌肉结合位点观察到相反的情况，即3H-ACh可被纳摩尔范围的阿托品和后马托品取代，但仅能被微摩尔范围的东莨菪碱取代。哌仑西平和4-二苯基乙酰氧基-N-甲基哌啶甲溴化物（4-DAMP）在纳摩尔至微摩尔范围内均可取代3H-ACh与两种组织的结合，且在内皮结合位点的取代发生在较低的配体浓度范围内。这两种化合物对平滑肌的表观IC50值分别比对内皮结合位点的表观IC50值大9倍和16倍。当用鸟苷酰亚胺二磷酸（GppNHp）饱和时，WKY的两种组织中均发生了高亲和力结合位点向低亲和力结合位点的转化，但仅在SHR的平滑肌中发生。GppNHp对3H-ACh与内皮结合位点的结合没有明显影响，证实SHR内皮中缺少3H-ACh的高亲和力位点。
