title: Opposite effects of anandamide and N-arachidonoyl dopamine in the regulation of prostaglandin E and 8-iso-PGF formation in primary glial cells.
abstract: It is widely accepted that neuroinflammation is a key player in various pathological events associated with brain injury. More specifically, glial activation and the subsequent release of pro-inflammatory cytokines, reactive oxygen species (ROS), and prostaglandins play a role of paramount importance in cerebral damage. In this study, we examined the role of two endocannabinoids, anandamide (AEA) and N-arachidonoyldopamine (NADA) in the regulation of prostaglandin E(2) (PGE(2)) synthesis in primary glial cells. We show that NADA is a potent inhibitor of PGE(2) synthesis in lipopolysaccharide (LPS) stimulated cells, without modifying the expression or enzymatic activity of COX-2 and the production of prostaglandin D(2). We also show that NADA has the ability to prevent the free radical formation in primary microglial cells. The key findings of this investigation are our observation that AEA and NADA have opposite effects on glial cells and, most importantly, the first description of NADA as a potential antioxidative and anti-inflammatory agent acting through a mechanism that involves reduction in the synthesis of microsomal prostaglandin E synthase in LPS-activated microglia. These findings provide new mechanistic insights into the anti-inflammatory activities of NADA in the CNS and its potential to design novel therapeutic strategies to manage neuroinflammatory diseases.
authors.affiliation: Departamento de Biología Celular, Fisiología e Immunología, Universidad de Córdoba, Spain.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Navarrete
authors.forename: Bernd L
authors.initials: BL
authors.lastname: Fiebich
authors.forename: Amaya García
authors.initials: AG
authors.lastname: de Vinuesa
authors.forename: Sandra
authors.initials: S
authors.lastname: Hess
authors.forename: Antonio C P
authors.initials: AC
authors.lastname: de Oliveira
authors.forename: Eduardo
authors.initials: E
authors.lastname: Candelario-Jalil
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Caballero
authors.forename: Marco A
authors.initials: MA
authors.lastname: Calzado
authors.forename: Eduardo
authors.initials: E
authors.lastname: Muñoz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D001095:Arachidonic Acids / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D063388:Endocannabinoids; D007536:Isomerism; D028421:Isoprostanes / Q000096:biosynthesis* / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D053284:Polyunsaturated Alkamides / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001095:Arachidonic Acids; D063388:Endocannabinoids; D028421:Isoprostanes; D053284:Polyunsaturated Alkamides; C474941:arachidonyl dopamine; D015232:Dinoprostone; C078814:anandamide; D004298:Dopamine; C011987:8-isoprostaglandin E2