Evidence for nociceptin/orphanin FQ (NOP) but not μ (MOP), δ (DOP) or κ (KOP) opioid receptor mRNA in whole human blood
Evidence for nociceptin/orphanin FQ (NOP) but not μ (MOP), δ (DOP) or κ (KOP) opioid receptor mRNA in whole human blood
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DOI：
10.1093/bja/aev540
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发表时间：
2016-03-01
影响因子：
9.8
通讯作者：
Lambert, D. G.
中科院分区：
文献类型：
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作者：
Al-Hashimi, M.;McDonald, J.;Lambert, D. G.
背景：虽然阿片类药物抑制免疫系统是众所周知的，但这种抑制作用的作用部位存在很大争议。免疫调节可以直接发生在免疫细胞或通过下丘脑-垂体-肾上腺轴中枢。在许多使用个体富集的免疫细胞群的研究中，我们未能检测到经典的A μ（MOP）、δ（DOP）和κ（KOP）受体。迄今为止，非经典的伤害感受素/FQ（N/OFQ）受体（NOP）在所有检查的细胞上表达。我们的假设是，免疫细胞不表达经典的阿片受体和使用全血将明确回答这个问题。方法：全血（含有所有免疫细胞类型）孵育阿片类药物（吗啡和芬太尼）通常遇到麻醉和模仿败血症的代理人[脂多糖（LPS）和肽聚糖G（PepG）]。阿片受体mRNA的表达进行了评估，通过终点聚合酶链反应（PCR）与凝胶可视化和定量PCR.Results：经典MOP，DOP，和KOP受体未检测到在任何测试的样品中，无论是在休息或挑战时与阿片类药物，LPS或PepG。DOP的商业引物在定量PCR中表现不佳，因此使用传统的基于凝胶的方法确认不存在表达。NOP受体在所有样品中检测;表达不受阿片类药物和LPS/PepG combination.Conclusions减少：经典阿片受体不表达循环免疫细胞。
WBackground: While it is well known that opioids depress the immune system, the site(s) of action for this depression is highly controversial. Immune modulation could occur directly at the immune cell or centrally via the hypothalamic-pituitary-adrenal axis. In a number of studies using individual enriched immune cell populations we have failed to detect classical A mu (MOP), delta (DOP) and kappa (KOP) receptors. The non-classical nociceptin/orphanin FQ (N/OFQ) receptor (NOP) is expressed on all cells examined thus far. Our hypothesis was that immune cells do not express classical opioid receptors and that using whole blood would definitively answer this question.Methods: Whole blood (containing all immune cell types) was incubated with opioids (morphine and fentanyl) commonly encountered in anaesthesia and with agents mimicking sepsis [lipopolysaccharide (LPS) and peptidoglycan G (PepG)]. Opioid receptor mRNA expression was assessed by endpoint polymerase chain reaction (PCR) with gel visualisation and quantitative PCR.Results: Classical MOP, DOP, and KOP receptors were not detected in any of the samples tested either at rest or when challenged with opioids, LPS or PepG. Commercial primers for DOP did not perform well in quantitative PCR, so the absence of expression was confirmed using a traditional gel-based approach. NOP receptors were detected in all samples; expression was unaffected by opioids and reduced by LPS/PepG combinations.Conclusions: Classical opioid receptors are not expressed on circulating immune cells.