Regulation of CCL2/MCP-1 production in astrocytes by desipramine and atomoxetine: Involvement of α2 adrenergic receptors.
Summary of "Regulation of CCL2/MCP-1 production in astrocytes by desipramine and atomoxetine: Involvement of α2 adrenergic receptors."
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.
Affiliation
Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), 28040 Madrid, Spain.
Journal Details
This article was published in the following journal.
Name: Brain research bulletin
ISSN: 1873-2747
Pages: 326-33
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21963947
- DOI: http://dx.doi.org/10.1016/j.brainresbull.2011.09.014
Medical and Biotech [MESH] Definitions
Desipramine
A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.
Receptors, Ccr2
CCR receptors with specificity for CHEMOKINE CCL2 and several other CCL2-related chemokines. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; MACROPHAGES; BASOPHILS; and NK CELLS.
Gliosis
The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.
Adrenergic Agents
Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters.
Adrenergic Antagonists
Drugs that bind to but do not activate ADRENERGIC RECEPTORS. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters EPINEPHRINE and NOREPINEPHRINE.
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