title: Norepinephrine enhances the LPS-induced expression of COX-2 and secretion of PGE2 in primary rat microglia.
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital of Freiburg, Freiburg, Germany.
authors.forename: Johannes C M
authors.initials: JC
authors.lastname: Schlachetzki
authors.forename: Bernd L
authors.initials: BL
authors.lastname: Fiebich
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Haake
authors.forename: Antonio C P
authors.initials: AC
authors.lastname: de Oliveira
authors.forename: Eduardo
authors.initials: E
authors.lastname: Candelario-Jalil
authors.forename: Michael T
authors.initials: MT
authors.lastname: Heneka
authors.forename: Michael
authors.initials: M
authors.lastname: Hüll
mesh_terms: 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
chemical_list: 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