Opposite effects of anandamide and n-arachidonoyl dopamine in the regulation of prostaglandin E₂ and 8-iso-PGF₂α formation in primary glial cells

• Published in: Journal of neurochemistry Vol. 109; no. 2; pp. 452 - 464
• Main Authors: Navarrete, Carmen M, Fiebich, Bernd L, de Vinuesa, Amaya García, Hess, Sandra, de Oliveira, Antonio C.P, Candelario-Jalil, Eduardo, Caballero, Francisco J, Calzado, Marco A, Muñoz, Eduardo
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.04.2009; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: 8-iso-PGF₂α; 8‐iso‐PGF2α; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Fundamental and applied biological sciences. Psychology; glial cells; Isolated neuron and nerve. Neuroglia; microsomal prostaglandin E synthase 1; n-arachidonoyl dopamine; neuroglia; neuroinflammation; prostaglandin E; prostaglandin E2; Vertebrates: nervous system and sense organs; glial cells; microsomal prostaglandin E synthase 1; Neuroglia; Prostaglandin E2; Activation; Free radical; n-arachidonoyl dopamine; Enzymatic activity; neuroinflammation; Eicosanoid; Lipopolysaccharide; Prostaglandin E; Release; 8-iso-PGF2α; Nervous system diseases; Glial cell; Oxygen; Dopamine; Arachidonic acid derivatives; Cytokine; Prostaglandin D2; Catecholamine; Cerebral disorder; Central nervous system disease; Neurotransmitter
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.05966.x

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 E₂ (PGE₂) synthesis in primary glial cells. We show that NADA is a potent inhibitor of PGE₂ synthesis in lipopolysaccharide (LPS) stimulated cells, without modifying the expression or enzymatic activity of COX-2 and the production of prostaglandin D₂. 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.