The Central Cannabinoid Receptor (CB1) Mediates Inhibition of Nitric Oxide Production by Rat Microglial Cells

摘要: Upon activation, brain microglial cells release proinflammatory mediators, such as nitric oxide (NO), which may play an important role in the central nervous system antibacterial, antiviral, and antitumor activities. However, excessive of NO has been postulated to elicit immune-mediated neurodegenerative inflammatory processes cause injury. In present study, effect cannabinoids on from endotoxin/cytokine-activated rat cortical was evaluated. A drug dose-dependent (0.1 microM-8 microM) inhibition exerted by cannabinoid receptor high-affinity binding enantiomer (-)-CP55940. contrast, a minimal inhibitory lower affinity paired (+)-CP56667. Pretreatment with Galphai/Galphao protein inactivator pertussis toxin, cyclic AMP reconstitution cell-permeable analog dibutyryl-cAMP, or treatment Galphas activator cholera resulted reversal (-)-CP55940-mediated release. similar effected when were pretreated (CB1) selective antagonist SR141716A. Mutagenic reverse transcription-polymerase chain reaction, Western immunoblot assay using CB1 amine terminal domain-specific antibody, cellular colocalization marker Griffonia simplicifolia isolectin B4 confirmed expression cells. Collectively, these results indicate functional linkage between cannabinoid-mediated production