A unique role for cAMP signaling in microglia during opioid tolerance and withdrawal.
A unique role for cAMP signaling in microglia during opioid tolerance and withdrawal.
复制标题
阿片类药物耐受和戒断期间小胶质细胞中 cAMP 信号传导的独特作用。
DOI：
10.1038/s41386-023-01685-2
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Neumaier,JohnF
中科院分区：
文献类型：
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作者：
Coffey,KevinR;Neumaier,JohnF
环磷酸腺苷（cAMP）信号转导的上调已被认为是阿片类药物耐受和戒断的一般机制[1]。通过腺苷酸环化酶产生的cAMP由G蛋白偶联受体调节，G蛋白偶联受体最终增加（Gs）或降低（Gi）神经元兴奋性。阿片样物质激活抑制cAMP信号传导的Gi偶联μ阿片样物质受体（M0R）。由于慢性阿片类药物暴露诱导耐受性，cAMP信号传导和相关基因在莫尔致密脑区（包括蓝斑和延髓核）中上调[1]。上调的基因包括cAMP反应元件结合蛋白（CREB）[1]、GS偶联受体（Adora2a、Drd1）和cAMP信号传导调节剂（Arpp21等）。[2]的文件。在神经元中，这些适应对抗阿片作用（耐受性），并在莫尔激活突然中断时驱动戒断症状。
Upregulation of cyclic adenosine monophosphate (cAMP) signaling has been proposed as a general mechanism of opioid tolerance and withdrawal [1]. cAMP production via adenylyl cyclase is regulated by G protein-coupled receptors which ultimately increase (Gs) or decrease (Gi) neuronal excitability. Opioids activate Gi-coupled μopioid receptors (MORs) which inhibit cAMP signaling. As chronic opioid exposure induces tolerance, cAMP signaling and related genes are upregulated in MOR dense brain regions including the locus coeruleus and nucleus accumbens [1]. Upregulated genes include cAMP Response Element-Binding Protein (CREB)[1], Gs-coupled receptors (Adora2a, Drd1), and modulators of cAMP signaling (Arpp21, etc.)[2]. In neurons, these adaptations oppose opioid action (tolerance) and drive withdrawal symptoms upon abrupt discontinuation of MOR activation.