Pharmacological profiles of opioid ligands at kappa opioid receptors.
Pharmacological profiles of opioid ligands at kappa opioid receptors.
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DOI：
10.1186/1471-2210-6-3
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发表时间：
2006-01-25
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影响因子：
--
通讯作者：
Lameh, Jelveh
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文献类型：
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作者：
Gharagozlou, Parham;Hashemi, Ezzat;Lameh, Jelveh
背景技术背景：本研究的目的是描述一组阿片类药物，包括部分激动剂，在人胚胎肾细胞系统中稳定表达的小鼠κ-阿片受体的活性。通过测量由5 μ M毛喉素刺激的环腺苷一磷酸（cAMP）产生的抑制来评估受体活化。这些配体的内在活性和效力被确定相对于内源性配体强啡肽和kappa激动剂具有最高的内在活性，在这项研究中，fentanyl.RESULTS：在研究的配体中，纳曲酮，WIN 44，441和曲马多辛，被归类为拮抗剂，而其余的配体是激动剂。通过测定毛喉素刺激的cAMP产生的抑制程度来评估激动剂的内在活性。每种配体抑制cAMP产生的绝对水平用于描述激动剂内在活性的等级顺序;芬太尼=洛芬太尼>或=氢吗啡酮=吗啡=纳洛啡>或=埃托啡>或= xorphanol >或= metazocine >或= SKF 10047 =环唑辛>或=布托啡诺>纳布啡。这些配体的亲和力大小顺序为：环唑辛>纳洛酮>或= SKF 10047 >或= xorphanol >或= WIN 44，441>纳洛啡>布托啡诺>纳布啡>或=洛芬太尼>洛佐辛>或=美他唑辛>或=吗啡>氢吗啡酮>芬太尼。这些结果阐明了一组阿片配体在κ-阿片受体的相对活性，并可以作为系统研究的初始步骤，从而了解这些阿片配体在该受体的作用模式。
BACKGROUND: The aim of the present study was to describe the activity of a set of opioid drugs, including partial agonists, in a human embryonic kidney cell system stably expressing only the mouse kappa-opioid receptors. Receptor activation was assessed by measuring the inhibition of cyclic adenosine mono phosphate (cAMP) production stimulated by 5 microM forskolin. Intrinsic activities and potencies of these ligands were determined relative to the endogenous ligand dynorphin and the kappa agonist with the highest intrinsic activity that was identified in this study, fentanyl.RESULTS: Among the ligands studied naltrexone, WIN 44,441 and dezocine, were classified as antagonists, while the remaining ligands were agonists. Intrinsic activity of agonists was assessed by determining the extent of inhibition of forskolin-stimulated cAMP production. The absolute levels of inhibition of cAMP production by each ligand was used to describe the rank order of intrinsic activity of the agonists; fentanyl = lofentanil > or = hydromorphone = morphine = nalorphine > or = etorphine > or = xorphanol > or = metazocine > or = SKF 10047 = cyclazocine > or = butorphanol > nalbuphine. The rank order of affinity of these ligands was; cyclazocine > naltrexone > or = SKF 10047 > or = xorphanol > or = WIN 44,441 > nalorphine > butorphanol > nalbuphine > or = lofentanil > dezocine > or = metazocine > or = morphine > hydromorphone > fentanyl.CONCLUSION: These results elucidate the relative activities of a set of opioid ligands at kappa-opioid receptor and can serve as the initial step in a systematic study leading to understanding of the mode of action of these opioid ligands at this receptor.