Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid and Centro de Investigación Biomédica en Red de Salud Mental, 28040 Madrid, Spain.
Brain Res Bull. 2011 Nov 25;86(5-6):326-33. doi: 10.1016/j.brainresbull.2011.09.014. Epub 2011 Sep 24.
Having previously observed that noradrenaline activation of β adrenergic receptors induces the synthesis of the chemokine monocyte chemoattractant protein (CCL2/MCP-1) in astrocytes, it is our interest to analyze the mechanisms involved in this process, particularly the possible effect of noradrenaline-modulating drugs. The treatment of primary rat astrocyte cultures with the noradrenaline transporter inhibitors desipramine or atomoxetine induced the expression and synthesis of CCL2/MCP-1 in these cells. This effect of both drugs in vitro suggests that CCL2/MCP-1 expression could also be modulated by some mechanism independent of the elevation of brain noradrenaline levels. This was confirmed by measuring a reduction in CCL2/MCP-1 production by the treatment with the α2 adrenergic receptor agonist clonidine. Accordingly, the blockade of α2 adrenergic receptors with yohimbine potentiated the production of MCP-1 stimulated by the activation of β receptors. While the activation of β adrenergic receptors and the subsequent elevation of cAMP levels seem to be the main pathway for noradrenaline to induce CCL2/MCP-1 in astrocytes, our data indicate that the α2 adrenergic receptors also regulate CCL2/MCP-1 expression working as inhibitory mediators.
先前观察到去甲肾上腺素激活β肾上腺素能受体可诱导星形胶质细胞中趋化因子单核细胞趋化蛋白-1（CCL2/MCP-1）的合成，我们的研究兴趣在于分析这一过程中涉及的机制，特别是去甲肾上腺素调节药物的可能作用。去甲肾上腺素转运体抑制剂丙咪嗪或托莫西汀处理原代大鼠星形胶质细胞培养物可诱导这些细胞中 CCL2/MCP-1 的表达和合成。这两种药物在体外的这种作用表明，CCL2/MCP-1 的表达也可能通过某种独立于脑去甲肾上腺素水平升高的机制来调节。用α2 肾上腺素能受体激动剂可乐定处理可证实这一点，可乐定可降低 CCL2/MCP-1 的产生。因此，用育亨宾阻断α2 肾上腺素能受体可增强β受体激活刺激产生的 MCP-1。虽然β肾上腺素能受体的激活和随后 cAMP 水平的升高似乎是去甲肾上腺素诱导星形胶质细胞中 CCL2/MCP-1 的主要途径，但我们的数据表明，α2 肾上腺素能受体也作为抑制性介质调节 CCL2/MCP-1 的表达。
