Zhu Liang, Cui Yong-Yao, Feng Ju-Mei, Wu Xing-Jun, Chen Hong-Zhuan
Institute of Drug Research, Shanghai Second Medical University, 280 South Chongqing Road, Shanghai 200025, China.
Life Sci. 2006 Feb 28;78(14):1617-23. doi: 10.1016/j.lfs.2005.07.034. Epub 2005 Oct 17.
The relationship between muscarinic receptor affinity states and the contractile response to the muscarinic agonists carbachol, aceclidine, and pilocarpine, has been examined in the isolated rabbit iris muscle. Contraction of the iris muscle by carbachol and aceclidine was more potent and/or more efficacious than the response to pilocarpine. Analysis of [3H]-Quinuclidinyl benzilate (QNB) binding showed that while both carbachol and aceclidine bound to high- and low-affinity forms of the muscarinic receptor, pilocarpine bound to one affinity state. The efficacy of carbachol and aceclidine to stimulate contraction of the iris muscle was consistent with receptor occupancy theory only when considering the low-affinity state of the muscarinic receptor, and activation of the low-affinity rather than high-affinity binding state of the receptor is likely to mediate the contraction of iris muscle. Therefore, the typical anti-glaucoma muscarinic agonists aceclidine and pilocarpine may interact differently with their target receptors in isolated rabbit iris muscle.
已在离体兔虹膜肌中研究了毒蕈碱受体亲和力状态与对毒蕈碱激动剂卡巴胆碱、醋克利定和毛果芸香碱的收缩反应之间的关系。卡巴胆碱和醋克利定引起的虹膜肌收缩比毛果芸香碱引起的反应更强效和/或更有效。[3H]-喹核醇基苯甲酸酯（QNB）结合分析表明，虽然卡巴胆碱和醋克利定都与毒蕈碱受体的高亲和力和低亲和力形式结合，但毛果芸香碱只与一种亲和力状态结合。仅当考虑毒蕈碱受体的低亲和力状态时，卡巴胆碱和醋克利定刺激虹膜肌收缩的效力才与受体占领理论一致，并且受体低亲和力而非高亲和力结合状态的激活可能介导虹膜肌收缩。因此，典型的抗青光眼毒蕈碱激动剂醋克利定和毛果芸香碱在离体兔虹膜肌中可能与其靶受体有不同的相互作用
