Nociceptin/orphanin FQ knockout mice display up-regulation of the opioid receptor-like 1 receptor and alterations in opioid receptor expression in the brain
Nociceptin/orphanin FQ knockout mice display up-regulation of the opioid receptor-like 1 receptor and alterations in opioid receptor expression in the brain
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DOI：
10.1016/s0306-4522(02)00750-9
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Kitchen, I
中科院分区：
文献类型：
--
作者：
Clarke, S;Chen, Z;Kitchen, I
阿片受体样1受体是阿片受体家族的新成员，其内源性肽配体被称为伤害感受肽和孤啡肽FQ。当这种肽在脊髓上给予时，在体内通过伤害感受肽/孤啡肽 FQ 激活类阿片受体 I 受体，产生痛觉过敏，但在脊髓水平给予镇痛。伤害感受肽/孤啡肽 FQ 还可以逆转应激引起的镇痛，表明该肽具有抗阿片类药物的特性。伤害感受肽/孤啡肽 FQ 敲除小鼠表现出疼痛敏感性和应激反应的改变，并表现出吗啡依赖性增加，表明伤害感受肽/孤啡肽 FQ 系统与经典阿片受体功能存在相互作用。为了确定伤害感受肽/孤啡肽 FQ 敲除小鼠的行为表型是否反映了阿片受体样 1 或经典阿片受体表达的变化，我们对这些动物大脑中的阿片受体样 1、mu、δ 和 kappa 阿片受体进行了定量放射自显影。使用[H-3]伤害感受肽、[H-3][D-Ala(2)-N-甲基-Phe(4)-Gly(5) ol]脑啡肽、[H-3]deltorphin-I或[H-3]nociceptin在野生型、杂合子和纯合子小鼠的冠状切片上测量受体密度[H-3](-)-N-methyl-N-[7-(1-吡咯烷基)-1-oxospiro[4,5]dec-8-yl]-4-苯并呋喃乙酰胺分别标记阿片受体样 1、mu-、delta- 和 kappa-受体。在纯合子小鼠的大脑中发现阿片受体样 1 受体的区域特异性上调（高达 135%）。 mu 受体也显示出基因型之间的显着差异，而 δ 和 κ 受体的变化较小。总之，阿片类受体样 1 受体的区域特异性上调表明伤害感受肽/孤啡肽 FQ 在某些大脑结构中具有补强作用，并且可能表明该肽调节这些区域的受体表达。阿片受体样 1 受体的变化可能与这些动物的焦虑表型有关，但观察到的 mu 受体的变化与吗啡反应的改变无关。 (C) 2003 国际广播组织。由爱思唯尔科学有限公司出版。保留所有权利。
The opioid receptor-like 1 receptor is a novel member of the opioid receptor family and its endogenous peptide ligand has been termed nociceptin and orphanin FQ. Activation of the opioid receptor-like I receptor by nociceptin/orphanin FQ in vivo produces hyperalgesia when this peptide is given supraspinally but analgesia at the spinal level. Nociceptin/orphanin FQ also reverses stress-induced analgesia, suggesting that the peptide has anti-opioid properties. Nociceptin/orphanin FQ knockout mice show alterations in pain sensitivity and stress responses and display increased morphine dependence, suggesting an interaction of the nociceptin/orphanin FQ system with classical opioid receptor function. To determine if the behavioural phenotype of nociceptin/orphanin FQ knockout mice reflects changes in either opioid receptor-like 1 or classical opioid receptor expression, we have carried out quantitative autoradiography of the opioid receptor-like 1, mu-, delta- and kappa-opiold receptors in the brains of these animals. Receptor density was measured on coronal sections from wild-type, heterozygous and homozygous mice using [H-3]nociceptin, [H-3][D-Ala(2)-N-methyl-Phe(4)-Gly(5) ol] enkephalin, [H-3]deltorphin-I, or [H-3](-)-N-methyl-N-[7-(1-pyrrodinyl)-1-oxospiro[4,5]dec-8-yl]-4-benzofuranacetamide to label opioid receptor-like 1, mu-, delta- and kappa-receptors, respectively. A region-specific up-regulation of the opioid receptor-like 1 receptor (up to 135%) was seen in brains from homozygous mice. mu-Receptors also showed significant differences between genotypes whilst changes in delta- and kappa-receptors were minor. In conclusion the region-specific up-regulation of the opioid receptor-like 1 receptor indicates a tonic role for nociceptin/orphanin FQ in some brain structures and may suggest the peptide regulates the receptor expression in these regions. The changes in the opioid receptor-like 1 receptor may relate to the anxiogenic phenotype of these animals but the observed change in mu-receptors does not correlate with altered morphine responses. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.