Grana E, Lucchelli A, Zonta F, Boselli C
Naunyn Schmiedebergs Arch Pharmacol. 1987 Jan;335(1):8-11. doi: 10.1007/BF00165028.
This study was undertaken to determine dissociation constants (KA and relative efficacies (er) of seven muscarinic agonists (methylfurtrethonium; dioxolane, oxathiolane, carbachol, muscarine, muscarone and oxotremorine) in three isolated tissues (guinea-pig ileum and atria and rat urinary bladder). The rank order of affinities (-log KA) of the various compounds varied depending on the tissue used. er values for the different agonists did not differ significantly from each other in any of the three tissues, except that the er of muscarine in the guinea-pig ileum was higher than those of the other compounds and that of oxotremorine in the rat urinary bladder was lower than those of the other agonists. Comparisons among tissues show that KA and er values were the same in different tissues for some compounds (muscarone, muscarine and methylfurtrethonium), while significant differences were found for the other compounds. This suggests the existence of a discrete receptor population recognized by some but not all agonists. For oxotremorine er as well as -log KA, is greater in atria than in smooth muscle: these factors combine to determine the cardioselectivity of this compound which can now ascribed to receptor selectivity.
本研究旨在测定七种毒蕈碱激动剂（甲基呋索氯铵、二氧戊环、氧硫杂环戊烷、卡巴胆碱、毒蕈碱、毒蝇蕈酮和氧化震颤素）在三种离体组织（豚鼠回肠、心房和大鼠膀胱）中的解离常数（KA）和相对效能（er）。不同化合物的亲和力（-log KA）排序因所用组织而异。除了豚鼠回肠中毒蕈碱的er高于其他化合物，以及大鼠膀胱中氧化震颤素的er低于其他激动剂外，三种组织中不同激动剂的er值彼此之间没有显著差异。组织间比较表明，某些化合物（毒蝇蕈酮、毒蕈碱和甲基呋索氯铵）在不同组织中的KA和er值相同，而其他化合物则存在显著差异。这表明存在一些但不是所有激动剂都能识别的离散受体群体。对于氧化震颤素，心房中的er以及-log KA大于平滑肌中的：这些因素共同决定了该化合物的心脏选择性，现在可以归因于受体选择性。
