The NOP receptor (nociceptin/orphanin FQ opioid peptide receptor) is the most recently discovered member of the opioid receptor family and, together with its endogenous ligand, N/OFQ, make up the fourth members of the opioid receptor and opioid peptide family. Because of its more recent discovery, an understanding of the cellular and behavioral actions induced by NOP receptor activation are less well developed than for the other members of the opioid receptor family. All of these factors are important because NOP receptor activation has a clear modulatory role on mu opioid receptor-mediated actions and thereby affects opioid analgesia, tolerance development, and reward. In addition to opioid modulatory actions, NOP receptor activation has important effects on motor function and other physiologic processes. This review discusses how NOP pharmacology intersects, contrasts, and interacts with the mu opioid receptor in terms of tertiary structure and mechanism of receptor activation; location of receptors in the central nervous system; mechanisms of desensitization and downregulation; cellular actions; intracellular signal transduction pathways; and behavioral actions with respect to analgesia, tolerance, dependence, and reward. This is followed by a discussion of the agonists and antagonists that have most contributed to our current knowledge. Because NOP receptors are highly expressed in brain and spinal cord and NOP receptor activation sometimes synergizes with mu receptor-mediated actions and sometimes opposes them, an understanding of NOP receptor pharmacology in the context of these interactions with the opioid receptors will be crucial to the development of novel therapeutics that engage the NOP receptor.

中文翻译：

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Nociceptin / Orphanin FQ受体的结构，信号传导，配体，功能以及与阿片类药物系统的相互作用。

NOP受体（nociceptin / orphanin FQ阿片肽受体）是阿片受体家族中最新发现的成员，并且与它的内源性配体N / OFQ一起构成了阿片受体和阿片肽家族的第四位成员。由于其最近的发现，与阿片受体家族的其他成员相比，对由NOP受体激活引起的细胞和行为作用的了解还不够完善。所有这些因素都很重要，因为NOP受体激活对阿片类阿片受体介导的作用具有明显的调节作用，从而影响阿片类镇痛，耐受性发展和报酬。除阿片样物质的调节作用外，NOP受体的活化对运动功能和其他生理过程也有重要影响。这篇综述从三级结构和受体激活机制的角度讨论了NOP药理学如何与mu阿片受体相交，形成对比并相互作用。受体在中枢神经系统中的位置；脱敏和下调的机制；细胞动作；细胞内信号转导途径；和有关镇痛，耐受性，依赖性和奖励的行为。接下来是对最有助于我们目前知识的激动剂和拮抗剂的讨论。由于NOP受体在脑和脊髓中高度表达，并且NOP受体激活有时与mu受体介导的作用协同作用，有时则与它们相反，