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

Chiba, Toshiki; Ueno, Sanae; Obara, Yutaro; Nakahata, Norimichi

doi:10.1111/j.2042-7158.2011.01250.x

Cited by 15 publications

(7 citation statements)

References 46 publications

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“…PC12 cells express GPR55 mRNA, but not CB 1 or CB 2 mRNA, whereas rat cerebellar granule neurons express both GPR55 and CB 1 as we recently reported [27]. PC12 cells also expressed GPR55 protein as mouse 3T3-L1 adipocytes (Figure 1b).…”

Section: Resultssupporting

confidence: 66%

Lysophosphatidylinositol Causes Neurite Retraction via GPR55, G13 and RhoA in PC12 Cells

et al. 2011

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GPR55 was recently identified as a putative receptor for certain cannabinoids, and lysophosphatidylinositol (LPI). Recently, the role of cannabinoids as GPR55 agonists has been disputed by a number of reports, in part, because studies investigating GPR55 often utilized overexpression systems, such as the GPR55-overexpressing HEK293 cells, which make it difficult to deduce the physiological role of endogenous GPR55. In the present study, we found that PC12 cells, a neural model cell line, express endogenous GPR55, and by using these cells, we were able to examine the role of endogenous GPR55. Although GPR55 mRNA and protein were expressed in PC12 cells, neither CB1 nor CB2 mRNA was expressed in these cells. GPR55 was predominantly localized on the plasma membrane in undifferentiated PC12 cells. However, GPR55 was also localized in the growth cones or the ruffled border in differentiated PC12 cells, suggesting a potential role for GPR55 in the regulation of neurite elongation. LPI increased intracellular Ca2+ concentration and RhoA activity, and induced ERK1/2 phosphorylation, whereas endogenous and synthetic cannabinoids did not, thereby suggesting that cannabinoids are not GPR55 agonists. LPI also caused neurite retraction in a time-dependent manner accompanied by the loss of neurofilament light chain and redistribution of actin in PC12 cells differentiated by NGF. This LPI-induced neurite retraction was found to be Gq-independent and G13-dependent. Furthermore, inactivation of RhoA function via C3 toxin and GPR55 siRNA knockdown prevented LPI-induced neurite retraction. These results suggest that LPI, and not cannabinoids, causes neurite retraction in differentiated PC12 cells via a GPR55, G13 and RhoA signaling pathway.

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Section: Resultssupporting

confidence: 66%

Lysophosphatidylinositol Causes Neurite Retraction via GPR55, G13 and RhoA in PC12 Cells

et al. 2011

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“…Furthermore, CDB decreased TNF-a, IL-6 and chemokines (MCP-1 and MIP-2) in a murine model of acute lung injury (Ribeiro et al, 2012); synthetic cannabinoid inhibited TNF-a, IL-1b and IL-6 expression induced by lipopolysaccharide in rat cerebellar granule cells (Chiba et al, 2011). CBD reduced blood brain-barrier alterations and prevented endothelial inflammatory response in arteriolar and venular vasodilation, induced by lipopolysaccharide (Ruiz-Valdepeñ as et al, 2011).…”

Section: Discussionmentioning

confidence: 96%

Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis

Barichello

Ceretta

Generoso

et al. 2012

European Journal of Pharmacology

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Pneumococcal meningitis is a life-threatening disease characterized by an acute infection affecting the pia matter, arachnoid and subarachnoid space. The intense inflammatory response is associated with a significant mortality rate and neurologic sequelae, such as, seizures, sensory-motor deficits and impairment of learning and memory. The aim of this study was to evaluate the effects of acute and extended administration of cannabidiol on pro-inflammatory cytokines and behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis. Male Wistar rats underwent a cisterna magna tap and received either 10μl of sterile saline as a placebo or an equivalent volume of S. pneumoniae suspension. Rats subjected to meningitis were treated by intraperitoneal injection with cannabidiol (2.5, 5, or 10mg/kg once or daily for 9 days after meningitis induction) or a placebo. Six hours after meningitis induction, the rats that received one dose were killed and the hippocampus and frontal cortex were obtained to assess cytokines/chemokine and brain-derived neurotrophic factor levels. On the 10th day, the rats were submitted to the inhibitory avoidance task. After the task, the animals were killed and samples from the hippocampus and frontal cortex were obtained. The extended administration of cannabidiol at different doses reduced the TNF-α level in frontal cortex. Prolonged treatment with canabidiol, 10mg/kg, prevented memory impairment in rats with pneumococcal meningitis. Although descriptive, our results demonstrate that cannabidiol has anti-inflammatory effects in pneumococcal meningitis and prevents cognitive sequel.

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“…Studies in rodent CNS also showed a wide expression Gpr55 mRNA in hippocampus, thalamus, forebrain, frontal cortex, hypothalamus, cerebellum and striatum (Chiba et al 2011, Sylantyev et al 2013, Wu et al 2013, Méndez-Díaz et al 2016, and GPR55 mRNA has also been found in monkey striatum (Martinez-Pinilla et al 2014). In addition, there is evidence that GPR55 is expressed at the protein level in the dorsal root ganglia neurons, where its activation enhances the excitability of sensory neurons (Lauckner et al 2008).…”

Section: Distribution Of Gpr55 In Humans and Rodentsmentioning

confidence: 94%

GPR55: a new promising target for metabolism?

Tudurí

Imbernón

Hernández-Bautista

et al. 2017

Journal of Molecular Endocrinology

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GPR55 is a G-protein-coupled receptor (GPCR) that has been identified as a new cannabinoid receptor. Given the wide localization of GPR55 in brain and peripheral tissues, this receptor has emerged as a regulator of multiple biological actions. Lysophosphatidylinositol (LPI) is generally accepted as the endogenous ligand of GPR55. In this review, we will focus on the role of GPR55 in energy balance and glucose metabolism. We will summarize its actions on feeding, nutrient partitioning, gastrointestinal motility and insulin secretion in preclinical models and the scarce data available in humans. The potential of GPR55 to become a new pharmaceutical target to treat obesity and type 2 diabetes, as well as the foreseeing difficulties are also discussed.

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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: 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.

Cited by 15 publications

References 46 publications

Lysophosphatidylinositol Causes Neurite Retraction via GPR55, G13 and RhoA in PC12 Cells

Lysophosphatidylinositol Causes Neurite Retraction via GPR55, G13 and RhoA in PC12 Cells

Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis

GPR55: a new promising target for metabolism?

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