Takayanagi I, Harada M, Koike K
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Jpn J Pharmacol. 1991 May;56(1):23-31. doi: 10.1254/jjp.56.23.
Concentration-response curves of 4 muscarinic full agonists were progressively inhibited by 10 to 50-min treatments of the longitudinal muscle of guinea pig ileum with propylbenzilylcholine mustard (PrBCM, 3 x 10(-6) M). A 90-min treatment with PrBCM had no further significant inhibitory effect on their curves. The 50-min treatment with PrBCM (3 x 10(-6) M) completely inhibited the concentration-response curves of 6 partial agonists. The limiting effect of PrBCM observed on the concentration-response curves of the full agonists was not found on the curves of the partial agonists. These results suggest that there are two subtypes of M3-cholinoceptors, PrBCM-sensitive receptors and PrBCM-resistant ones. Pilocarpine, a partial agonist, shifted the concentration-response curve of carbachol, a full agonist, in a parallel fashion in the strips treated with PrBCM (3 x 10(-6) M) for 50 min, suggesting that an interaction of pilocarpine with PrBCM-resistant cholinoceptors does not induce contraction. The full agonists contract the longitudinal muscle through the interaction of two cholinoceptors, PrBCM-sensitive and -resistant ones, while the partial agonists produce the contraction through the activation of PrBCM-sensitive ones.
用丙基苯甲酰胆碱氮芥（PrBCM，3×10⁻⁶ M）对豚鼠回肠纵肌进行10至50分钟的处理，可逐渐抑制4种毒蕈碱完全激动剂的浓度 - 反应曲线。用PrBCM处理90分钟对其曲线没有进一步的显著抑制作用。用PrBCM（3×10⁻⁶ M）处理50分钟可完全抑制6种部分激动剂的浓度 - 反应曲线。在部分激动剂的曲线上未发现PrBCM对完全激动剂浓度 - 反应曲线所观察到的极限效应。这些结果表明存在两种M3 - 胆碱能受体亚型，即对PrBCM敏感的受体和对PrBCM耐药的受体。毛果芸香碱，一种部分激动剂，在用PrBCM（3×10⁻⁶ M）处理50分钟的条带上，以平行方式移动了完全激动剂卡巴胆碱的浓度 - 反应曲线，这表明毛果芸香碱与对PrBCM耐药的胆碱能受体相互作用不会诱导收缩。完全激动剂通过两种胆碱能受体（对PrBCM敏感的和耐药的）的相互作用使纵肌收缩，而部分激动剂通过激活对PrBCM敏感的受体产生收缩。
