Molecular mechanisms of opioid receptor-dependent signaling and behavior.
Molecular mechanisms of opioid receptor-dependent signaling and behavior.
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DOI：
10.1097/aln.0b013e318238bba6
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发表时间：
2011-12
期刊：
影响因子：
8.8
通讯作者：
Bruchas MR
中科院分区：
文献类型：
--
作者：
Al-Hasani R;Bruchas MR
阿片受体已被靶向用于治疗疼痛和相关疾病数千年，并且仍然是临床上最广泛使用的镇痛药。Mu（μ）、kappa（κ）和delta（δ）阿片受体代表最初分类的受体亚型，其中阿片受体样-1（ORL 1）的特征最少。所有四种受体都是G蛋白偶联的，并激活抑制性G蛋白。这些受体形成同源和异源二聚体复合物，向激酶级联传递信号，并为各种蛋白质提供支架。在这篇综述中，我们讨论了经典的机制和发展，了解阿片耐受，阿片受体信号，并强调阿片分子药理学，行为药理学和人类遗传学的进展。我们将阿片受体信号传导如何导致行为的调节与治疗干预的潜力结合起来。最后，我们得出结论，有一个持续的需要更多的阿片受体在体内的翻译工作。
Opioid receptors have been targeted for the treatment of pain and related disorders for thousands of years, and remain the most widely used analgesics in the clinic. Mu (μ), kappa (κ), and delta (δ) opioid receptors represent the originally classified receptor subtypes, with opioid receptor like-1 (ORL1) being the least characterized. All four receptors are G-protein coupled, and activate inhibitory G-proteins. These receptors form homo- and hetereodimeric complexes, signal to kinase cascades, and scaffold a variety of proteins. In this review, we discuss classical mechanisms and developments in understanding opioid tolerance, opioid receptor signaling, and highlight advances in opioid molecular pharmacology, behavioral pharmacology, and human genetics. We put into context how opioid receptor signaling leads to the modulation of behavior with the potential for therapeutic intervention. Finally, we conclude that there is a continued need for more translational work on opioid receptors in vivo.