Activation of mu opioid receptors inhibits microglial cell chemotaxis.
Activation of mu opioid receptors inhibits microglial cell chemotaxis.
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发表时间：
1997-05
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通讯作者：
C. Chao;Shuxian Hu;Katherine B. Shark;W. Sheng;G. Gekker;Phillip K. Peterson
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作者：
C. Chao;Shuxian Hu;Katherine B. Shark;W. Sheng;G. Gekker;Phillip K. Peterson
阿片类药物调节巨噬细胞的多种功能。小胶质细胞，常驻的巨噬细胞，迁移到中枢神经系统内的炎症部位。利用设计用于跨越人类大脑mu阿片受体（MOR）的整个开放阅读框架的引物集，我们发现小胶质细胞组成性地表达MOR mRNA。小胶质细胞中MOR开放阅读框的cDNA序列与人脑组织相同。利用富集的人胎儿小胶质细胞培养物，我们发现吗啡以剂量依赖的方式有效抑制小胶质细胞向C5a的定向迁移（趋化性），IC50值为1 fM吗啡。我们还发现，选择性MOR配体DAMGO可以剂量依赖性地抑制小胶质细胞趋化性，IC50值为1 nM， 10 nM的β -funaltrexamine可显著减弱该值。综上所述，这些发现表明，组成性表达的MOR的激活抑制了小胶质细胞的趋化性，并支持了MOR在大脑中具有抗炎作用的概念。
Opiates modulate many macrophage functions. Microglia, the resident macrophages of the brain, migrate to sites of inflammation within the CNS. Using primer sets designed to span the entire open reading frame of the human brain mu opioid receptor (MOR), we found that microglial cells constitutively expressed MOR mRNA. The cDNA sequences of the MOR open reading frame in microglia were identical to those of human brain tissue. Using enriched human fetal microglial cell cultures, we found that morphine potently inhibited the directed migration (chemotaxis) of microglial cells toward C5a in a dose-dependent manner with an IC50 value of 1 fM morphine. We also found that DAMGO, a selective MOR ligand, dose-dependently suppressed microglial cell chemotaxis with an IC50 value of 1 nM, which was significantly attenuated by 10 nM beta-funaltrexamine. Taken together, these findings suggest that activation of constitutively expressed MOR inhibits microglial cell chemotaxis and support the notion of an anti-inflammatory role of MOR within the brain.