β-arrestins: regulatory role and therapeutic potential in opioid and cannabinoid receptor-mediated analgesia.
β-arrestins: regulatory role and therapeutic potential in opioid and cannabinoid receptor-mediated analgesia.
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DOI：
10.1007/978-3-642-41199-1_22
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发表时间：
2014
影响因子：
--
通讯作者：
Bohn LM
中科院分区：
文献类型：
--
作者：
Raehal KM;Bohn LM
疼痛是一种复杂的疾病，神经化学和心理成分导致疼痛的严重性、持续性和难以充分治疗。阿片类药物和大麻素是两类镇痛药，几个世纪以来一直用于治疗疼痛，可以说是人类使用的最古老的“药理学”干预措施。不幸的是，它们也会产生一些不良副作用，使疼痛管理复杂化。阿片类物质和大麻素作用于G蛋白偶联受体（GPCR），并且它们的大部分作用分别由μ-阿片受体（莫尔）和大麻素CB 1受体（CB 1 R）介导。这些受体与细胞内第二信使和调节蛋白偶联以赋予其生物学效应。在本章中，我们回顾了细胞内调节蛋白，β-arrestins，在调节莫尔和CB 1 R的作用，以及它们如何影响阿片类药物和大麻素类药物在体内的镇痛和副作用。这篇文献综述表明，阿片类药物和大麻素激动剂的开发使莫尔和CB 1 R偏向G蛋白信号级联，远离β-抑制蛋白相互作用，这可能提供一种新的机制，通过这种机制产生镇痛作用，不良反应不太严重。
Pain is a complex disorder with neurochemical and psychological components contributing to the severity, the persistence, and the difficulty in adequately treating the condition. Opioid and cannabinoids are two classes of analgesics that have been used to treat pain for centuries and are arguably the oldest of “pharmacological” interventions used by man. Unfortunately, they also produce several adverse side effects that can complicate pain management. Opioids and cannabinoids act at G protein-coupled receptors (GPCRs), and much of their effects are mediated by the mu-opioid receptor (MOR) and cannabinoid CB1 receptor (CB1R), respectively. These receptors couple to intracellular second messengers and regulatory proteins to impart their biological effects. In this chapter, we review the role of the intracellular regulatory proteins, β-arrestins, in modulating MOR and CB1R and how they influence the analgesic and side-effect profiles of opioid and cannabinoid drugs in vivo. This review of the literature suggests that the development of opioid and cannabinoid agonists that bias MOR and CB1R toward G protein signaling cascades and away from β-arrestin interactions may provide a novel mechanism by which to produce analgesia with less severe adverse effects.