Regulation of CCL2/MCP-1 production in astrocytes by desipramine and atomoxetine: Involvement of α2 adrenergic receptors

Having previously observed that noradrenaline activation of beta 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 alpha 2 adrenergic receptor agonist clonidine. Accordingly, the blockade of alpha 2 adrenergic receptors with yohimbine potentiated the production of MCP-1 stimulated by the activation of beta receptors. While the activation of beta 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 alpha 2 adrenergic receptors also regulate CCL2/MCP-1 expression working as inhibitory mediators. (C) 2011 Elsevier Inc. All rights reserved.