Norepinephrine enhances the LPS-induced expression of COX-2 and secretion of PGE2 in primary rat microglia.
BACKGROUND
Recent studies suggest an important role for neurotransmitters as modulators of inflammation. Neuroinflammatory mediators such as cytokines and molecules of the arachidonic acid pathway are generated and released by microglia. The monoamine norepinephrine reduces the production of cytokines by activated microglia in vitro. However, little is known about the effects of norepinephrine on prostanoid synthesis. In the present study, we investigate the role of norepinephrine on cyclooxygenase- (COX-)2 expression/synthesis and prostaglandin (PG)E2 production in rat primary microglia.


RESULTS
Interestingly, norepinephrine increased COX-2 mRNA, but not protein expression. Norepinephrine strongly enhanced COX-2 expression and PGE2 production induced by lipopolysaccharide (LPS). This effect is likely to be mediated by beta-adrenoreceptors, since beta-, but not alpha-adrenoreceptor agonists produced similar results. Furthermore, beta-adrenoreceptor antagonists blocked the enhancement of COX-2 levels induced by norepinephrine and beta-adrenoreceptor agonists.


CONCLUSIONS
Considering that PGE2 displays different roles in neuroinflammatory and neurodegenerative disorders, norepinephrine may play an important function in the modulation of these processes in pathophysiological conditions.
Schlachetzki
Johannes C M
JC
Department of Psychiatry and Psychotherapy, University Hospital of Freiburg, Freiburg, Germany.
Fiebich
Bernd L
BL
Haake
Elisabeth
E
de Oliveira
Antonio C P
AC
Candelario-Jalil
Eduardo
E
Heneka
Michael T
MT
Hüll
Michael
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D007124:Immunoenzyme Techniques / Q000379:methods; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D008070:Lipopolysaccharides; D011412:Propanolamines; D012333:RNA, Messenger; C026777:ICI 118551; C049763:CGP 20712A; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D009638:Norepinephrine