Role of CB1 and CB2 receptors in the inhibitory effects of cannabinoids on lipopolysaccharide-induced nitric oxide release in astrocyte cultures

Francisco Molina-Holgado, Eduardo Molina-Holgado, Carmen Guaza, Nancy J. Rothwell

Research output: Contribution to journalArticlepeer-review

Abstract

The purpose of this study was to investigate the role of the central cannabinoid receptor (CB1) 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 CB1 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 CB2 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 CB1 receptors may promote antiinflammatory responses in astrocytes. © 2002 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)829-836
Number of pages7
JournalJournal of Neuroscience Research
Volume67
Issue number6
DOIs
Publication statusPublished - 15 Mar 2002

Keywords

  • CB1 cannabinoid receptor
  • Murine astrocyte cultures
  • Nitric oxide

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