Department of Psychiatry and Psychotherapy, University Hospital of Freiburg, Freiburg, Germany.
J Neuroinflammation. 2010 Jan 11;7:2. doi: 10.1186/1742-2094-7-2.
Recent studies suggest an important role for neurotransmitters as modulators of inflammation. Neuroinflammatory mediators such as cytokines and molecules of the arachidonic acid pathway are generated and released by microglia. The monoamine norepinephrine reduces the production of cytokines by activated microglia in vitro. However, little is known about the effects of norepinephrine on prostanoid synthesis. In the present study, we investigate the role of norepinephrine on cyclooxygenase- (COX-)2 expression/synthesis and prostaglandin (PG)E2 production in rat primary microglia.
Interestingly, norepinephrine increased COX-2 mRNA, but not protein expression. Norepinephrine strongly enhanced COX-2 expression and PGE2 production induced by lipopolysaccharide (LPS). This effect is likely to be mediated by beta-adrenoreceptors, since beta-, but not alpha-adrenoreceptor agonists produced similar results. Furthermore, beta-adrenoreceptor antagonists blocked the enhancement of COX-2 levels induced by norepinephrine and beta-adrenoreceptor agonists.
Considering that PGE2 displays different roles in neuroinflammatory and neurodegenerative disorders, norepinephrine may play an important function in the modulation of these processes in pathophysiological conditions.
最近的研究表明，神经递质作为炎症调节剂的作用非常重要。神经炎症介质，如细胞因子和花生四烯酸途径的分子，由小胶质细胞产生和释放。单胺去甲肾上腺素可减少体外激活的小胶质细胞中细胞因子的产生。然而，关于去甲肾上腺素对前列腺素合成的影响知之甚少。在本研究中，我们研究了去甲肾上腺素对大鼠原代小胶质细胞中环氧化酶-（COX-）2 表达/合成和前列腺素（PG）E2 产生的作用。
有趣的是，去甲肾上腺素增加了 COX-2 mRNA，但不增加蛋白表达。去甲肾上腺素强烈增强了脂多糖（LPS）诱导的 COX-2 表达和 PGE2 产生。这种作用可能是通过β-肾上腺素受体介导的，因为β-，而不是α-肾上腺素受体激动剂产生了类似的结果。此外，β-肾上腺素受体拮抗剂阻断了去甲肾上腺素和β-肾上腺素受体激动剂诱导的 COX-2 水平的增强。
考虑到 PGE2 在神经炎症和神经退行性疾病中具有不同的作用，去甲肾上腺素在病理生理条件下可能对这些过程的调节起着重要作用。
