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Cannabinoid-mediated Inhibition of Inducible Nitric Oxide Production by Rat Microglial Cells: Evidence for CB1 Receptor Participation

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Neuroimmune Circuits, Drugs of Abuse, and Infectious Diseases

Abstract

Activated brain microglial cells release inflammatory mediators such as nitric oxide (NO) that may play important roles in central nervous system antibacterial, antiviral, and antitumor activities. However, excessive release of these factors has been postulated to elicit immunemediated neurodegenerative inflammatory processes and to cause brain injury. Recent studies using the rat animal model indicate that select cannabinoids may modulate production of these inflammatory factors. Treatment of neonatal rat brain cortical microglial cells with the cannabinoid paired enantiomers CP55940 and CP56667 resulted in a stereoselective differential effect on inducible NO production. The analog CP55940 exerted a dose-dependent inhibition of interferon gamma (IFNγ)/bacterial lipopolysaccharide (LPS)-inducible NO production which was significantly greater than that exerted by CP56667. Pretreatment of microglial cells with the CB 1 cannabinoid receptor-selective antagonist SR141716A reversed this CP55940-mediated inhibition. MRT-PCR demonstrated the presence of CB 1 receptor mRNA within microglial cells consistent with the presence of CB 1 receptors. Collectively, these results indicate that the cannabinoid analog CP55940 selectively inhibits inducible NO production by microglial cells and that this inhibition is effected, at least in part, through the CB 1 receptor.

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© 2002 Kluwer Academic Publishers

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Cabral, G.A., Harmon, K.N., Carlisle, S.J. (2002). Cannabinoid-mediated Inhibition of Inducible Nitric Oxide Production by Rat Microglial Cells: Evidence for CB1 Receptor Participation. In: Friedman, H., Klein, T.W., Madden, J.J. (eds) Neuroimmune Circuits, Drugs of Abuse, and Infectious Diseases. Advances in Experimental Medicine and Biology, vol 493. Springer, Boston, MA. https://doi.org/10.1007/0-306-47611-8_24

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  • DOI: https://doi.org/10.1007/0-306-47611-8_24

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-46466-9

  • Online ISBN: 978-0-306-47611-2

  • eBook Packages: Springer Book Archive

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