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目的：研究κ阿片受体及其与非肽类激动剂的作用机制．方法：以细菌视紫红质为模板，模建κ阿片受体七个跨膜区的三维结构；将五个高活性非肽类激动剂对接到螺旋区内，研究作用机制．结果：（１）四氢吡咯环氮原子与Ａｓｐ１３８羧基成氢键；（２）乙酰胺羰基氧与受体Ｓｅｒ１８７间存在氢键作用；（３）与乙酰胺相连的疏水基团处于由Ｖａｌ２３９、Ｖａｌ２３６、Ｐｈｅ２３５、Ｖａｌ２３２、Ｌｅｕ１８６和Ｔｒｐ１８３构成的疏水区域内；（４）激动剂的四氢吡咯环为Ｉｌｅ２９０、Ａｓｐ１３８、Ｉｌｅ１９４、Ｉｌｅ１３５和Ｃｙｓ１３１残基包围．结论：模型将有助于设计新型高效安全的κ阿片受体激动剂．
AIM: To investigate the mechanism of action of κ opioid receptor and its interaction with non-peptide agonists. METHODS: Bacteriorhodopsin was used as a template to model the three-dimensional structure of the seven transmembrane regions of kappa opioid receptors. Five highly active non-peptide agonists were docked into the helical region to study the mechanism of action. Results: (1) Hydrogen bonding between the pyrrolidine ring nitrogen atom and Asp138 carboxyl group; (2) Hydrogen bonding between acetamide carbonyl oxygen and acceptor Ser187; (3) Val236, Phe235, Val232, Leu186 and Trp183; and (4) the tetrahydropyrrole ring of the agonist is surrounded by Ile290, Asp138, Ile194, Ile135 and Cys131 residues. Conclusions: The model will help design a new and efficient kappa opioid receptor agonist.