King M A, Rossi G C, Chang A H, Williams L, Pasternak G W
George Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Neurosci Lett. 1997 Feb 21;223(2):113-6. doi: 10.1016/s0304-3940(97)13414-0.
Previous work reveals that orphanin FQ/nociceptin (OFQ/N) administered supraspinally produces an initial hyperalgesic response followed by analgesia. Spinally, OFQ/N elicits a rapidly appearing, naltrexone-reversible, dose-dependent analgesia in the tailflick assay without any indication of hyperalgesia. Two OFQ/N fragments, OFQ/N (1-7) and OFQ/N (1-11), are active, but far weaker. Blockade of sigma receptors with haloperidol enhances the analgesic potency of spinal OFQ/N, OFQ/N (1-7) and OFQ/N (1-11), but not as dramatically as supraspinal OFQ. Antisense probes targeting the second and third coding exons, but not the first exon, of the cloned mouse OFQ/N receptor (KOR-3) partially block OFQ/N analgesia.
先前的研究表明，孤啡肽/痛敏肽（OFQ/N）经脊髓上给药会产生最初的痛觉过敏反应，随后出现镇痛作用。在脊髓水平，OFQ/N在甩尾试验中引发快速出现的、纳曲酮可逆的、剂量依赖性镇痛，且没有任何痛觉过敏的迹象。两个OFQ/N片段，即OFQ/N（1-7）和OFQ/N（1-11）具有活性，但活性远低于OFQ/N。用氟哌啶醇阻断σ受体可增强脊髓OFQ/N、OFQ/N（1-7）和OFQ/N（1-11）的镇痛效力，但增强程度不如脊髓上给药的OFQ显著。针对克隆的小鼠OFQ/N受体（KOR-3）的第二和第三编码外显子而非第一外显子的反义探针可部分阻断OFQ/N的镇痛作用。
