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A synthetic cannabinoid, CP55940, inhibits lipopolysaccharide-induced cytokine mRNA expression in a cannabinoid receptor-independent mechanism in rat cerebellar granule cells.

Abstract

OBJECTIVES

The inflammatory response plays an important role in the pathogenesis of many diseases in the central nervous system. Cannabinoids exhibit diverse pharmacological actions including anti-inflammatory activity. In this study, we tried to elucidate possible effects of cannabinoids on lipopolysaccharide (LPS)-induced expression of inflammatory cytokine mRNAs in rat cerebellar granule cells.

METHODS

Inhibitory effects of cannabinoids on cytokine induction in cerebellar granule cells were determined by RT-PCR method.

KEY FINDINGS

In these cells, both mRNA and protein of cannabinoid receptor 1 (CB(1) ), but not CB(2) , were expressed. LPS (1 µg/ml) produced a marked increase in the induction of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumour necrosis factor-α. CP55940, a synthetic cannabinoid analogue, concentration-dependently inhibited inflammatory cytokine expression induced by LPS. On the other hand, the endocannabinoids 2-arachidonoylglycerol and anandamide were not able to inhibit this inflammatory response. Notably, a CB(1) /CB(2) antagonist NESS0327 (3 µm) did not reverse the inhibition of cytokine mRNA expression induced by CP55940. GPR55, a putative novel cannabinoid receptor, mRNA was also expressed in cerebellar granule cells. Although it has been suggested that G(q) associates with GPR55, cannabinoids including CP55940 did not promote phosphoinositide hydrolysis and consequent elevation of intracellular Ca([2+]) concentration. Furthermore, a putative GPR55 antagonist, cannabidiol, also showed a similar inhibitory effect to that of CP55940.

CONCLUSIONS

These results suggest that the synthetic cannabinoid CP55940 negatively modulates cytokine mRNA expression in cerebellar granule cells by a CB and GPR55 receptor-independent mechanism.

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  • Authors+Show Affiliations

    ,

    Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai, Japan.

    , ,

    Source

    MeSH

    Animals
    Anti-Inflammatory Agents
    Arachidonic Acids
    Calcium
    Cannabidiol
    Cannabinoid Receptor Antagonists
    Cannabinoid Receptor Modulators
    Cannabinoids
    Cerebellum
    Cyclohexanols
    Cytokines
    Dose-Response Relationship, Drug
    Endocannabinoids
    Glycerides
    Inflammation
    Lipopolysaccharides
    Piperidines
    Polyunsaturated Alkamides
    Pyrazoles
    RNA, Messenger
    Rats
    Rats, Sprague-Dawley
    Receptor, Cannabinoid, CB1
    Receptors, Cannabinoid
    Receptors, G-Protein-Coupled
    Reverse Transcriptase Polymerase Chain Reaction

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21492165

    Citation

    TY - JOUR T1 - A synthetic cannabinoid, CP55940, inhibits lipopolysaccharide-induced cytokine mRNA expression in a cannabinoid receptor-independent mechanism in rat cerebellar granule cells. AU - Chiba,Toshiki, AU - Ueno,Sanae, AU - Obara,Yutaro, AU - Nakahata,Norimichi, Y1 - 2011/03/28/ PY - 2011/3/28/aheadofprint PY - 2011/4/16/entrez PY - 2011/4/16/pubmed PY - 2011/12/13/medline SP - 636 EP - 47 JF - The Journal of pharmacy and pharmacology JO - J. Pharm. Pharmacol. VL - 63 IS - 5 N2 - OBJECTIVES: The inflammatory response plays an important role in the pathogenesis of many diseases in the central nervous system. Cannabinoids exhibit diverse pharmacological actions including anti-inflammatory activity. In this study, we tried to elucidate possible effects of cannabinoids on lipopolysaccharide (LPS)-induced expression of inflammatory cytokine mRNAs in rat cerebellar granule cells. METHODS: Inhibitory effects of cannabinoids on cytokine induction in cerebellar granule cells were determined by RT-PCR method. KEY FINDINGS: In these cells, both mRNA and protein of cannabinoid receptor 1 (CB(1) ), but not CB(2) , were expressed. LPS (1 µg/ml) produced a marked increase in the induction of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumour necrosis factor-α. CP55940, a synthetic cannabinoid analogue, concentration-dependently inhibited inflammatory cytokine expression induced by LPS. On the other hand, the endocannabinoids 2-arachidonoylglycerol and anandamide were not able to inhibit this inflammatory response. Notably, a CB(1) /CB(2) antagonist NESS0327 (3 µm) did not reverse the inhibition of cytokine mRNA expression induced by CP55940. GPR55, a putative novel cannabinoid receptor, mRNA was also expressed in cerebellar granule cells. Although it has been suggested that G(q) associates with GPR55, cannabinoids including CP55940 did not promote phosphoinositide hydrolysis and consequent elevation of intracellular Ca([2+]) concentration. Furthermore, a putative GPR55 antagonist, cannabidiol, also showed a similar inhibitory effect to that of CP55940. CONCLUSIONS: These results suggest that the synthetic cannabinoid CP55940 negatively modulates cytokine mRNA expression in cerebellar granule cells by a CB and GPR55 receptor-independent mechanism. SN - 2042-7158 UR - https://www.unboundmedicine.com/medline/citation/21492165/abstract/A_synthetic_cannabinoid_CP55940_inhibits_lipopolysaccharide_induced_cytokine_mRNA_expression_in_a_cannabinoid_receptor_independent_mechanism_in_rat_cerebellar_granule_cells_ L2 - http://dx.doi.org/10.1111/j.2042-7158.2011.01250.x ER -