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首页> 外文期刊>Neuron >Functional dissociation of mu opioid receptor signaling and endocytosis: implications for the biology of opiate tolerance and addiction (see comments)
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Functional dissociation of mu opioid receptor signaling and endocytosis: implications for the biology of opiate tolerance and addiction (see comments)

机译：mu阿片受体信号转导和内吞作用的功能解离：对阿片耐受性和成瘾的生物学意义（见评论）

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摘要

Opiate analgesia, tolerance, and addiction are mediated by drug-induced activation of the mu opioid receptor. A fundamental question in addiction biology is why exogenous opiate drugs have a high liability for inducing tolerance and addiction while native ligands do not. Studies indicate that highly addictive opiate drugs such as morphine are deficient in their ability to induce the desensitization and endocytosis of receptors. Here, we demonstrate that this regulatory mechanism reveals an independent functional property of opiate drugs that can be distinguished from previously established agonist properties. Moreover, this property correlates with agonist propensity to promote physiological tolerance, suggesting a fundamental revision of our understanding of the role of receptor endocytosis in the biology of opiate drug action and addiction.
机译：阿片类镇痛，耐受性和成瘾作用是由药物诱导的阿片类阿片受体激活引起的。成瘾生物学中的一个基本问题是，为什么外源性阿片药物在诱导耐受性和成瘾方面具有很高的责任，而天然配体却没有。研究表明，高度成瘾的阿片类药物（如吗啡）缺乏诱导受体脱敏和内吞作用的能力。在这里，我们证明了这种调节机制揭示了鸦片药物的独立功能特性，可以与先前建立的激动剂特性区分开。而且，该特性与激动剂促进生理耐受性的倾向有关，表明我们对鸦片药物作用和成瘾生物学中受体内吞作用的理解有了根本性的修正。

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