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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.
J Pharm Pharmacol 2011; 63(5):636-47JP

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.

Authors+Show Affiliations

Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21492165

Citation

Chiba, Toshiki, et al. "A Synthetic Cannabinoid, CP55940, Inhibits Lipopolysaccharide-induced Cytokine mRNA Expression in a Cannabinoid Receptor-independent Mechanism in Rat Cerebellar Granule Cells." The Journal of Pharmacy and Pharmacology, vol. 63, no. 5, 2011, pp. 636-47.
Chiba T, Ueno S, Obara Y, et al. A synthetic cannabinoid, CP55940, inhibits lipopolysaccharide-induced cytokine mRNA expression in a cannabinoid receptor-independent mechanism in rat cerebellar granule cells. J Pharm Pharmacol. 2011;63(5):636-47.
Chiba, T., Ueno, S., Obara, Y., & Nakahata, N. (2011). A synthetic cannabinoid, CP55940, inhibits lipopolysaccharide-induced cytokine mRNA expression in a cannabinoid receptor-independent mechanism in rat cerebellar granule cells. The Journal of Pharmacy and Pharmacology, 63(5), pp. 636-47. doi:10.1111/j.2042-7158.2011.01250.x.
Chiba T, et al. A Synthetic Cannabinoid, CP55940, Inhibits Lipopolysaccharide-induced Cytokine mRNA Expression in a Cannabinoid Receptor-independent Mechanism in Rat Cerebellar Granule Cells. J Pharm Pharmacol. 2011;63(5):636-47. PubMed PMID: 21492165.
* Article titles in AMA citation format should be in sentence-case
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 - 2011/4/16/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 - https://doi.org/10.1111/j.2042-7158.2011.01250.x DB - PRIME DP - Unbound Medicine ER -