Dauphin F, Ting V, Payette P, Dennis M, Hamel E
Laboratory of Cerebrovascular Research, Montreal Neurological Institute, Quebec, Canada.
Eur J Pharmacol. 1991 Aug 14;207(4):319-27. doi: 10.1016/0922-4106(91)90006-4.
The nature of the muscarinic receptor subtype mediating the acetylcholine (ACh)-induced constriction of the cat middle cerebral artery was investigated in vitro by recording the smooth muscle isometric tension of precontracted endothelium-denuded arterial segments. The ability of selective (pirenzepine, UH-AH 371, AF-DX 116, methoctramine, AQ-RA 741, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and hexahydro-sila-difenidol (HHSiD)) and non-selective (atropine) antagonists to inhibit the constriction elicited by ACh was estimated. In addition, using a subtype-specific ribonucleotide probe directed against mRNA encoding the human m1 (Hm1) muscarinic receptor, identification of the corresponding vascular receptor was undertaken in total RNA extracts from cat cerebral blood vessels. The potent inhibition of the ACh-induced constriction by M1 antagonists (pirenzepine and UH-AH 371; pA2 values respectively of 8.08 and 8.64), together with lower affinities of M2 (AF-DX 116; pA2 = 6.50, methoctramine; pA2 = 6.27 and AQ-RA 741; pA2 = 7.60) and M3 compounds (4-DAMP and HHSiD; with pA2 values of 8.85 and 7.76, respectively) strongly suggested the involvement of a pharmacological M1 receptor in this vasomotor response. Furthermore, Northern blot hybridization with the selective Hm1 ribonucleotide probe showed the presence of mRNA transcripts for this muscarinic receptor subtype in the cat cerebrovascular bed. The results indicate that muscarinic constriction in the feline cerebrovascular bed is mediated by a pharmacological M1 receptor subtype and that the corresponding m1 receptor mRNA is present in cat cerebral blood vessels. These findings clearly point to a role of M1 muscarinic receptors in cerebrovascular function.
通过记录预先收缩的去内皮动脉段的平滑肌等长张力，在体外研究了介导乙酰胆碱（ACh）诱导的猫大脑中动脉收缩的毒蕈碱受体亚型的性质。评估了选择性拮抗剂（哌仑西平、UH-AH 371、AF-DX 116、甲溴东莨菪碱、AQ-RA 741、4-二苯基乙酰氧基-N-甲基哌啶甲碘化物（4-DAMP）和六氢硅二苯二醇（HHSiD））和非选择性拮抗剂（阿托品）抑制ACh引起的收缩的能力。此外，使用针对编码人m1（Hm1）毒蕈碱受体的mRNA的亚型特异性核糖核苷酸探针，在猫脑血管的总RNA提取物中对相应的血管受体进行鉴定。M1拮抗剂（哌仑西平与UH-AH 371；pA2值分别为8.08和8.64）对ACh诱导的收缩有强效抑制作用，同时M2化合物（AF-DX 116；pA2 = 6.50、甲溴东莨菪碱；pA2 = 6.27和AQ-RA 741；pA2 = 7.60）和M3化合物（4-DAMP和HHSiD；pA2值分别为8.85和7.76）的亲和力较低，这强烈表明药理学上的M1受体参与了这种血管运动反应。此外，用选择性Hm1核糖核苷酸探针进行的Northern印迹杂交显示，在猫脑血管床中存在该毒蕈碱受体亚型的mRNA转录本。结果表明，猫脑血管床中的毒蕈碱收缩是由药理学上的M1受体亚型介导的，并且相应的m1受体mRNA存在于猫脑血管中。这些发现清楚地表明M1毒蕈碱受体在脑血管功能中起作用。
