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Role of CB 1 and CB 2 receptors in the inhibitory effects of cannabinoids on lipopolysaccharide‐induced nitric oxide release in astrocyte cultures
Author(s) -
MolinaHolgado Francisco,
MolinaHolgado Eduardo,
Guaza Carmen,
Rothwell Nancy J.
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10165
Subject(s) - astrocyte , inhibitory postsynaptic potential , nitric oxide , cannabinoid receptor , lipopolysaccharide , receptor , chemistry , pharmacology , neuroscience , biology , antagonist , biochemistry , immunology , central nervous system , organic chemistry
Abstract The purpose of this study was to investigate the role of the central cannabinoid receptor (CB 1 ) in mediating the actions of the endogenous cannabinoid agonist anandamide and the synthetic cannabinoid CP‐55940. Activation of primary mouse astrocyte cultures by exposure to bacterial lipopolysaccharide (LPS) caused a marked (approximately tenfold) increase in nitric oxide (NO) release. Coincubation with the cannabinoid agonists anandamide or CP‐55940 markedly inhibited release of NO (–12% to –55%). This effect was abolished by SR‐141716A (1 μM), a CB 1 receptor antagonist. SR‐141716A alone also significantly increased NO release in response to LPS, suggesting that endogenous cannabinoids modify inflammatory responses. In contrast, coincubation with the CB 2 receptor antagonist SR‐144528 (1 μM) abolished the inhibitory effects of the endogenous cannabinoid anandamide on LPS‐induced NO release, although this may reflect nonspecific effects of this ligand or cannabinoid actions through atypical receptors of anandamide. We also showed that endogenous or synthetic cannabinoids inhibit LPS‐induced inducible NO synthase expression (mRNA and protein) in astrocyte cultures. These results indicate that CB 1 receptors may promote antiinflammatory responses in astrocytes. © 2002 Wiley‐Liss, Inc.