Wnendt S, Krüger T, Janocha E, Hildebrandt D, Englberger W
Department of Molecular Pharmacology, Grünenthal GmbH, Aachen, Germany.
Mol Pharmacol. 1999 Aug;56(2):334-8. doi: 10.1124/mol.56.2.334.
The role of the opioid-like receptor 1 (ORL1) and its endogenous ligand, nociceptin/orphanin FQ (N/OFQ), in nociception, anxiety, and learning remains to be defined. To allow the rapid identification of agonists and antagonists, a reporter gene assay has been established in which the ORL1 receptor is functionally linked to the cyclic AMP-dependent expression of luciferase. N/OFQ and N/OFQ(1-13)NH(2) inhibited the forskolin-induced luciferase gene expression with IC(50) values of 0.81 +/- 0.5 and 0.87 +/- 0.16 nM, respectively. Buprenorphine was identified as a full agonist at the ORL1 receptor with an IC(50) value of 8.4 +/- 2.8 nM. Fentanyl and 7-benzylidenenaltrexone displayed a weak agonistic activity. The ORL1 antagonist [Phe(1)Psi(CH(2)-NH)Gly(2)]N/OFQ((1-13))NH(2) clearly behaved as an agonist in this assay with an IC(50) value of 85 +/- 47 nM. Thus, there is still a need for antagonistic tool compounds that might help to elucidate the neurophysiological role of N/OFQ.
阿片样受体1（ORL1）及其内源性配体孤啡肽/痛敏肽（N/OFQ）在痛觉、焦虑和学习中的作用仍有待明确。为了能够快速鉴定激动剂和拮抗剂，已建立了一种报告基因检测方法，其中ORL1受体与荧光素酶的环磷酸腺苷依赖性表达功能相关联。N/OFQ和N/OFQ(1 - 13)NH₂抑制福斯高林诱导的荧光素酶基因表达，IC₅₀值分别为0.81±0.5和0.87±0.16 nM。丁丙诺啡被鉴定为ORL1受体的完全激动剂，IC₅₀值为8.4±2.8 nM。芬太尼和7 - 亚苄基纳曲酮表现出较弱的激动活性。ORL1拮抗剂[Phe(1)Psi(CH₂ - NH)Gly(2)]N/OFQ((1 - 13))NH₂在该检测中明显表现为激动剂，IC₅₀值为85±47 nM。因此，仍然需要有助于阐明N/OFQ神经生理作用的拮抗工具化合物。
