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孤啡肽在大鼠脑内对抗吗啡镇痛

田今华, 许伟, 方圆, 韩济生

北京医科大学神经科学研究中心，北京100083.；Oregon Health Sciences University, Portland, OR 97201，USA

摘要

脑内全新的阿片受体样(opioid receptor-like, ORL)受体(1994)及其内源性配体(orphanin FQ,OFQ)孤啡肤(1995)的发现形成了中枢神经系统阿片/抗阿片相互关系的研究领域中一个新的推动力。基于它们与阿片家族的高同源性及在脑内痛觉整合相关区域的丰富表达，本实验观察了OFQ在大鼠脑内对吗啡镇痛作用的影响。结果表明:(1) OFQ可以对抗脑室注射生理盐水引起的镇痛，后者可能是一种由内源性阿片系统介导的应激镇痛。(2)脑室注射OFQ在很大的剂量范围(40 fmol到50 nmol)内能翻转吗啡镇痛。(3)用OFQ受体反义寡核昔酸阻断中枢ORL受体的表达，可加强吗啡的累加镇痛效应。提示孤啡肤在大鼠脑内很可能作为一种抗阿片肤发挥作用。

关键词： 阿片受体样受体; 孤啡肽; 吗啡镇痛; 反义寡核普酸

ANTAGONISTIC EFFECT OF ORPHANIN FQ ON MORPHINE ANALGESIA IN RAT BRAIN

TIAN JIN-HUA, XU WEI, FANG YUAN, HAN JI_SHENG

Neuroscience Research Center，Beijing Medical Gnuaersity, Beijing 100083；Oregon Health Sciences Universdy, Portland, OR 97201，USA)

Abstract

The discovery of a novel receptor-opioid receptor-like (ORL) receptor(1994)and its endogenous ligand-Orphanin FQ (OFQ)(1995) represented a new approach in the study of opioids and anti-opioids in CNS. Based on the high homology of ORL receptor and OFQ with their opioid family counterparts，as well as the high expression of ORL receptor mRNA and protein in the brain areas associated with nociception，the effect of OFQ on morphine induced analgesia in the rat brain was further investigated. The results showed that:(1)Intracerebroventricular (i. c. v.)injection of OFQ reversed the stress analgesia induced by i. c. v. injection of normal saline，which seems to be mediated by endogenous opioid peptides. (2) I. c. v. injection of OFQ dose-dependently antagonized morphine-induced analgesia dose-dependently. (3) I. c. v. injection of antisense oligodeoxynucleotide for the gene encoding ORL receptor to block the expression of ORL receptor in the CNS potentiated the analgesia induced by cumulative injection of morphine. The results suggest that OFQ seems to play a role of anti-opioid peptide in
the rat brain.

Key words: opioid receptor-like receptor;Orphanin FQ;Morphine analgesia;antisense oligodeoxynucleotide

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引用本文：

田今华, 许伟, 方圆, 韩济生. 孤啡肽在大鼠脑内对抗吗啡镇痛[J]. 生理学报 1997; 49 (2): .

TIAN JIN-HUA, XU WEI, FANG YUAN, HAN JI_SHENG. ANTAGONISTIC EFFECT OF ORPHANIN FQ ON MORPHINE ANALGESIA IN RAT BRAIN . Acta Physiol Sin 1997; 49 (2): (in Chinese with English abstract).