Clague R U, Eglen R M, Strachan A C, Whiting R L
Br J Pharmacol. 1985 Sep;86(1):163-70. doi: 10.1111/j.1476-5381.1985.tb09446.x.
The action of 'selective' agonists and antagonists at muscarinic receptors mediating ileal contractions, and the rate and force of atrial contractions has been assessed. The effect of nicotinic receptor stimulation, catecholamine release and acetylcholinesterase (AChE) action on muscarinic activity has also been assessed. The nicotinic actions of carbachol did not affect its agonist potency nor the antagonist affinity data obtained when this agonist was used in atrial and ileal preparations. Antagonist data indicated that muscarinic receptors mediating the rate and force of atrial contractions did not differ. Differences in agonist potencies at these two muscarinic receptors were attributable to either differences in intrinsic efficacy or susceptibility to the action of acetylcholinesterase. The small differences in agonist potency observed between atrial and ileal muscarinic receptors were considered not sufficient to indicate receptor heterogeneity. The pirenzepine affinity data indicated that all three receptors are of the M2 type. Affinity data using secoverine and 4-diphenyl-acetoxy-N-methyl piperidine methiodide indicated that ileal and atrial muscarinic receptors differ. Data obtained using gallamine, pancuronium and stercuronium cannot be regarded as indicative of receptor affinity since the antagonism is not competitive; it did nonetheless corroborate the conclusion that ileal and atrial muscarinic receptors are different.
已评估了“选择性”激动剂和拮抗剂对介导回肠收缩的毒蕈碱受体以及心房收缩的速率和力量的作用。还评估了烟碱样受体刺激、儿茶酚胺释放和乙酰胆碱酯酶（AChE）作用对毒蕈碱活性的影响。卡巴胆碱的烟碱样作用既不影响其激动剂效力，也不影响在心房和回肠制剂中使用该激动剂时获得的拮抗剂亲和力数据。拮抗剂数据表明，介导心房收缩速率和力量的毒蕈碱受体并无差异。这两种毒蕈碱受体激动剂效力的差异可归因于内在效能的差异或对乙酰胆碱酯酶作用的敏感性差异。在心房和回肠毒蕈碱受体之间观察到的激动剂效力的微小差异被认为不足以表明受体的异质性。哌仑西平的亲和力数据表明，所有三种受体均为M2型。使用西维美林和4 - 二苯基乙酰氧基 - N - 甲基哌啶甲碘化物获得的亲和力数据表明，回肠和心房毒蕈碱受体存在差异。使用加拉明、泮库溴铵和司可罗宁获得的数据不能被视为受体亲和力的指标，因为这种拮抗作用并非竞争性的；不过，它确实证实了回肠和心房毒蕈碱受体不同这一结论。
