Association of mu-opioid and NMDA receptors in the periaqueductal gray: what does it mean for pain control?
Association of mu-opioid and NMDA receptors in the periaqueductal gray: what does it mean for pain control?
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导水管周围灰质 mu-阿片类药物和 NMDA 受体的关联：对于疼痛控制意味着什么？
DOI：
10.1038/npp.2011.241
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Ingram,SusanL
中科院分区：
文献类型：
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作者：
Ingram,SusanL
大脑有一个内源性下行控制系统来调节疼痛。这一系统被认为是由中脑导水管周围灰质(PAG)中的输出神经元激活而产生的，该输出神经元投射到轮状腹侧延髓，继而传递到脊髓以调制传入的疼痛信号(Basbaum和Fields，1984)。电刺激或向PAG腹侧部分微量注射阿片类药物可产生镇痛作用。阿片类药物通过抑制紧张性GABA释放(或解除抑制)来激活该途径。去抑制假说认为，吗啡和谷氨酸通过激活不同的细胞群刺激下行通路，阿片类药物通过抑制GABA中间神经元或抑制性投射神经元进入PAG，谷氨酸通过直接激活PAG输出神经元来刺激下行通路。在这一期的《神经精神药理学》中，Rodriguez-Munoz等人提供了证据，证明了PAG中NMDA和mU-阿片(MOR)受体的密切联系，表明这两种受体不仅共存于同一细胞群体中，而且在急性吗啡耐受过程中存在NMDA/MOR相互作用的双向调节。Rodriguez-Munoz等人的论文的关键发现之一是，Mor蛋白和NMDA受体的NR1亚单位可以被针对MOR NR1上的细胞外表位的抗体免疫沉淀。这些结果表明，这两个蛋白质直接相互作用或作为多个蛋白质信号复合体的一部分相互作用。免疫沉淀研究得到了表面等离子体共振和双分子荧光互补分析的支持，表明这两种蛋白质的C末端可以直接结合在一起。Rodriguez-Munoz和他的同事的研究首次表明，含有MOR和NR1亚单位的蛋白质复合体在吗啡耐受过程中可能受到功能调节。以前通过电子显微镜分析在PAG神经元的树突中观察到MOR和NR1亚基的共存，但
The brain has an endogenous descending control system to modulate pain. This system is thought to arise from the activation of output neurons in the periaqueductal gray area (PAG) that project to the rostroventral medulla, with a relay to the spinal cord to modulate incoming pain signals (Basbaum and Fields, 1984). Electrical stimulation or microinjection of opioids into the ventral portion of the PAG results in analgesia. Opioids activate the pathway by inhibiting tonic GABA release (or disinhibition). The disinhibition hypothesis predicts that morphine and glutamate stimulate the descending pathway via activation of different cell populations, opioids by inhibiting GABA interneurons or inhibitory projection neurons into the PAG, and glutamate by directly activating PAG output neurons. In this issue of Neuropsychopharmacology, Rodriguez-Munoz et al provide evidence for a close association of NMDA and mu-opioid (MOR) receptors in the PAG, suggesting that these two receptors are not only colocalized within the same cell population, but that there is bidirectional regulation of the NMDA/MOR interaction during acute morphine tolerance.One of the key findings of the Rodriguez-Munoz et al’s paper is that MOR proteins and NR1 subunits of the NMDA receptor can be immunoprecipitated by antibodies specific for extracellular epitopes on either the MOR or NR1. These results suggest that the two proteins are directly interacting or interact as part of a signaling complex of multiple proteins. Immunoprecipitation studies are supported with surface plasmon resonance and bimolecular fluorescence complementation analyses, demonstrating that the C-terminal tails of the two proteins can directly bind to one another. The studies by Rodriguez-Munoz and colleagues are the first to suggest that protein complexes containing MOR and NR1 subunits may be functionally regulated during morphine tolerance. Colocalization of MOR and NR1 subunits has been previously observed with electron microscopic analyses in dendrites of PAG neurons, but