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Effect of anandamide uptake inhibition in the production of nitric oxide and in the release of cytokines in astrocyte cultures
Author(s) -
OrtegaGutiérrez Silvia,
MolinaHolgado Eduardo,
Guaza Carmen
Publication year - 2005
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20229
Subject(s) - proinflammatory cytokine , neuroinflammation , anandamide , astrocyte , nitric oxide , cannabinoid receptor , pharmacology , cannabinoid , nitric oxide synthase , endocannabinoid system , cannabinoid receptor type 2 , biology , agonist , inflammation , immunology , central nervous system , endocrinology , receptor , biochemistry
Astrocytes play a key role regulating aspects of inflammation in the central nervous system (CNS). Several enzymes, such as the inducible nitric oxide synthase (iNOS) or the cyclooxygenase‐2 (COX‐2), along with different inflammatory mediators such as the free radical nitric oxide (NO) or proinflammatory cytokines, have been proposed to be involved in the cell damage associated with neuroinflammation. Recent studies suggest that the endogenous cannabinoid system (ECS) may be involved in the regulation of neuroinflammation. Cannabinoid agonists decrease neurotoxicity and release of proinflammatory factors from activated glial cells and anandamide itself is able to promote antiinflammatory responses in astrocytes via CB 1 cannabinoid receptors. The present study is aimed at studying whether UCM707, a potent and selective anandamide uptake inhibitor, is able to inhibit the production of proinflammatory mediators by LPS‐stimulated astrocytes. Our findings indicate that UCM707 is able to reduce NO release, iNOS expression, and the production of the proinflammatory cytokines tumoral necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) in a significant manner, while producing a slight increase in IL‐6 levels. These effects can be reproduced by administration of the synthetic agonist HU210 and partially or totally blocked by administration of CB 1 or CB 2 selective antagonists, further supporting the involvement of the ECS. These results confirm the ability of UCM707 to reinforce the beneficial effects induced by anandamide and make it an attractive candidate for the management of those pathologies with neuroinflammation as one of their hallmarks. © 2005 Wiley‐Liss, Inc.