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在表达δ阿片受体的人胚肾细胞中阿片类配体的激活谱。

Activation profiles of opioid ligands in HEK cells expressing delta opioid receptors.

作者信息

Gharagozlou Parham, Demirci Hasan, Clark J David, Lameh Jelveh

机构信息

Molecular Research Institute, Mountain View, CA 94043, USA.

出版信息

BMC Neurosci. 2002 Nov 18;3:19. doi: 10.1186/1471-2202-3-19.

DOI:10.1186/1471-2202-3-19
PMID:12437765
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC137588/
Abstract

BACKGROUND

The aim of the present study was to characterize the activation profiles of 15 opioid ligands in transfected human embryonic kidney cells expressing only delta opioid receptors. Activation profiles of most of these ligands at delta opioid receptors had not been previously characterized in vitro. Receptor activation was assessed by measuring the inhibition of forskolin-stimulated cAMP production.

RESULTS

Naltrexone and nalorphine were classified as antagonists at delta opioid receptor. The other ligands studied were agonists at delta opioid receptors and demonstrated IC50 values of 0.1 nM to 2 microM, maximal inhibition of 39-77% and receptor binding affinities of 0.5 to 243 nM. The rank order of efficacy of the ligands tested was metazocine = xorphanol > or = fentanyl = SKF 10047 = etorphine = hydromorphone = butorphanol = lofentanil > WIN 44,441 = Nalbuphine = cyclazocine > or = met-enkephalin >> morphine = dezocine. For the first time these data describe and compare the function and relative efficacy of several ligands at delta opioid receptors.

CONCLUSIONS

The data produced from this study can lead to elucidation of the complete activation profiles of several opioid ligands, leading to clarification of the mechanisms involved in physiological effects of these ligands at delta opioid receptors. Furthermore, these data can be used as a basis for novel use of existing opioid ligands based on their pharmacology at delta opioid receptors.

摘要

背景

本研究的目的是描述15种阿片类配体在仅表达δ阿片受体的转染人胚肾细胞中的激活特征。这些配体中大多数在δ阿片受体上的激活特征此前尚未在体外进行过描述。通过测量对福司可林刺激的环磷酸腺苷（cAMP）产生的抑制作用来评估受体激活情况。

结果

纳曲酮和烯丙吗啡被归类为δ阿片受体拮抗剂。所研究的其他配体是δ阿片受体激动剂，其半数抑制浓度（IC50）值为0.1 nM至2 μM，最大抑制率为39% - 77%，受体结合亲和力为0.5至243 nM。所测试配体的效能排序为：美他佐辛 = 环佐辛 > 或 = fentanyl = SKF 10047 = 埃托啡 = 氢吗啡酮 = 布托啡诺 = 洛芬太尼 > WIN 44,441 = 纳布啡 = 环唑辛 > 或 = 甲硫氨酸脑啡肽 >> 吗啡 = 地佐辛。这些数据首次描述并比较了几种配体在δ阿片受体上的功能和相对效能。

结论

本研究产生的数据能够阐明几种阿片类配体的完整激活特征，从而澄清这些配体在δ阿片受体上产生生理效应所涉及的机制。此外，这些数据可作为基于其在δ阿片受体上的药理学特性对现有阿片类配体进行新用途开发的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8b/137588/def97c6710c5/1471-2202-3-19-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8b/137588/7b4104ebfe3e/1471-2202-3-19-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8b/137588/def97c6710c5/1471-2202-3-19-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8b/137588/7b4104ebfe3e/1471-2202-3-19-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea8b/137588/def97c6710c5/1471-2202-3-19-2.jpg

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