title: Regulation of CCL2/MCP-1 production in astrocytes by desipramine and atomoxetine: involvement of α2 adrenergic receptors.
abstract: 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.
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid and Centro de Investigación Biomédica en Red de Salud Mental, 28040 Madrid, Spain.
authors.forename: Ara E
authors.initials: AE
authors.lastname: Hinojosa
authors.forename: Borja
authors.initials: B
authors.lastname: García-Bueno
authors.forename: Juan C
authors.initials: JC
authors.lastname: Leza
authors.forename: José L M
authors.initials: JL
authors.lastname: Madrigal
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000069445:Atomoxetine Hydrochloride; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D018932:Chemokine CCL2; D011437:Propylamines; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D000069445:Atomoxetine Hydrochloride; D000242:Cyclic AMP; D007545:Isoproterenol; D003000:Clonidine; D003891:Desipramine; D009638:Norepinephrine