Effects of norepinephrine on rat cultured microglial cells that express alpha 1, alpha 2, beta 1 and beta 2 adrenergic receptors

• Published in: Neuropharmacology Vol. 43; no. 6; pp. 1026 - 1034
• Main Authors: Mori, Kohji, Ozaki, Emi, Zhang, Bo, Yang, Lihua, Yokoyama, Akiko, Takeda, Ikuko, Maeda, Nobuji, Sakanaka, Masahiro, Tanaka, Junya
• Format: Journal Article
• Language: English
• Published: 01.11.2002
• ISSN: 0028-3908
• DOI: 10.1016/S0028-3908(02)00211-3

Microglial cells rapidly become activated in response to even minor damage of neurons, suggestive of the intimate interactions between neurons and microglial cells. Although mediators for microglia-neuron interactions have not been well identified, neurotransmitters are possible candidates transmitting signals from neurons to microglial cells. Among the neurotransmitters, we focused on the effects of norepinephrine and other adrenergic agonists on the functions of rat cultured microglial cells. Reverse transcriptase polymerase chain reaction studies revealed that microglial cells expressed mRNAs encoding alpha 1A, alpha 2A, beta 1 and beta 2 receptors. Norepinephrine and a beta 2 adrenergic agonist terbutaline elevated intracellular cAMP level of microglial cells. Norepinephrine, an alpha 1 agonist phenylephrine, a beta 1 agonist dobutamine and terbutaline suppressed the expressions of mRNAs encoding pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor alpha . Release of tumor necrosis factor alpha and nitric oxide was suppressed by norepinephrine, phenylephrine, dobutamine and terbutaline. An alpha 2 agonist clonidine and dobutamine upregulated the expression of mRNA encoding catechol-O-methyl transferase, an important enzyme to degrade norepinephrine. Norepinephrine, dobutamine and terbutaline upregulated the expressions of mRNA encoding 3-phospshoglycerate dehydrogenase, an essential enzyme for synthesis of L-serine and glycine, which are amino acids necessary for neuronal survival. Clonidine upregulated the expression of mRNA encoding an anti-apoptotic factor Bcl-xL. These results suggest that norepinephrine participates in the regulation of brain function at least partly by modulating the functions of microglia.