Evidence for Cannabinoid Receptor-Dependent and -Independent Mechanisms of Action in Leukocytes

@article{Kaplan2003EvidenceFC,
  title={Evidence for Cannabinoid Receptor-Dependent and -Independent Mechanisms of Action in Leukocytes},
  author={Barbara L F Kaplan and Cheryl E. Rockwell and Norbert E. Kaminski},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2003},
  volume={306},
  pages={1077 - 1085}
}
Cannabinoids exhibit immunosuppressive actions that include inhibition of interleukin-2 production in response to a variety of T cell activation stimuli. Traditionally, the effects of these compounds have been attributed to cannabinoid receptors CB1 and CB2, both of which are expressed in mouse splenocytes. Therefore, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorphenyl)-4-methyl-H-pyrazole-3 carboxyamidehydrochloride (SR141716A), a CB1 antagonist, and N-[(1S)-endo-1,3,3,-trimethyl… 

Tables from this paper

A Cyclooxygenase Metabolite of Anandamide Causes Inhibition of Interleukin-2 Secretion in Murine Splenocytes

The present studies suggest that inhibition of interleukin-2 secretion by anandamide is independent of CB1/CB2 and the AMT/FAAH system, and suggest that inhibited by a PPARγ, which is activated by a cyclooxygenase-2 metabolite of an andamide.

A Novel Cannabinoid Peripheral Cannabinoid Receptor-Selective Inverse Agonist Blocks Leukocyte Recruitment in Vivo

  • C. LunnJ. Fine L. Bober
  • Chemistry, Biology
    Journal of Pharmacology and Experimental Therapeutics
  • 2006
It is concluded that selective cannabinoid CB2 inverse agonists may serve as novel immunomodulatory agents in the treatment of a broad range of acute and chronic inflammatory disorders in which leukocyte recruitment is a hallmark of disease pathology.

Cannabinoid-Mediated Elevation of Intracellular Calcium: A Structure-Activity Relationship

The present results demonstrate that classic tricyclic cannabinoids with structural similarity to Δ9-THC elicit a robust influx of calcium in T cells putatively through receptor-operated cation channels in a manner sensitive to the cannabinoid receptor antagonists, but independent of the CB1 and CB2 receptors.

Cannabinoid signalling in TNF-alpha induced IL-8 release.

Antitumor Effects of Cannabidiol, a Nonpsychoactive Cannabinoid, on Human Glioma Cell Lines

Evaluating the in vitro antiproliferative ability of cannabidiol (CBD), a nonpsychoactive cannabinoid compound, on U87 and U373 human glioma cell lines suggests a possible application of CBD as an antineoplastic agent.

A novel cannabinoid CB 2 receptor-selective inverse agonist blocks leukocyte recruitment in vivo

It is demonstrated that Sch.336 effectively blocks the migration of cells in response both to the cannabinoid agonist 2-arachidonylglycerol in vitro, and to more complex chemotactic signals in vivo, which indicates that CB 2 -selective inverse agonists may provide a novel immunotherapeutic treatment of inflammatory diseases.

Interleukin-2 Suppression by 2-Arachidonyl Glycerol Is Mediated through Peroxisome Proliferator-Activated Receptor γ Independently of Cannabinoid Receptors 1 and 2

PPARγ is identified as a novel intracellular target of 2-AG, which mediates the suppression of IL-2 by 2- AG in a manner that is independent of CB1 and/or CB2.

Cannabinoid receptor-mediated regulation of intracellular calcium by 9-tetrahydrocannabinol in T cells

Cannabinoids exhibit broad, immune, modulating activity by targeting many cell types within the immune system, including T cells, which exhibit sensitivity, as evidenced by altered activation,

Cannabinoids Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-κB and Interferon-β/STAT Proinflammatory Pathways in BV-2 Microglial Cells*

Observations show that CBD and THC vary in their effects on the anti-inflammatory pathways, including the NF-κB and IFNβ-dependent pathways.
...

References

SHOWING 1-10 OF 44 REFERENCES

Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB(2) receptor.

Evidence That the Cannabinoid CB1 Receptor Is a 2-Arachidonoylglycerol Receptor

The results strongly suggested that the cannabinoid CB1 receptor is originally a 2-arachidonoylglycerol receptor, and 2-Arachidonoyslglycersol is the intrinsic physiological ligand for the cannabinoidCB1 receptor.

Activation of the human peripheral cannabinoid receptor results in inhibition of adenylyl cyclase.

The results demonstrate that the CB2 receptor is functionally coupled to inhibition of adenylyl cyclase activity via a pertussis toxin-sensitive G protein.

Evidence That 2-Arachidonoylglycerol but Not N-Palmitoylethanolamine or Anandamide Is the Physiological Ligand for the Cannabinoid CB2 Receptor

2-arachidonoylglycerol is the most potent compound among a number of naturally occurring cannabimimetic molecules, and anandamide and N-palmitoylethanolamine, other putative endogenous ligands, were found to be a weak partial agonist and an inactive ligand, respectively.

Cannabinol-mediated inhibition of nuclear factor-kappaB, cAMP response element-binding protein, and interleukin-2 secretion by activated thymocytes.

Analysis of up-stream regulation revealed a decrease in phosphorylated CREB/ATF nuclear proteins in PMA/Io-activated thymocytes after CBN treatment, and CBN prevented the phosphorylation-dependent degradation of the nuclear factor-kappaB inhibitory protein IkappaB-alpha.

Structure of a cannabinoid receptor and functional expression of the cloned cDNA

The cloning and expression of a complementary DNA that encodes a G protein-coupled receptor that is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana are suggested.

Molecular characterization of a peripheral receptor for cannabinoids

The cloning of a receptor for cannabinoids is reported that is not expressed in the brain but rather in macrophages in the marginal zone of spleen, which helps clarify the non-psychoactive effects of cannabinoids.

Cannabinoid Inhibition of Adenylate Cyclase-mediated Signal Transduction and Interleukin 2 (IL-2) Expression in the Murine T-cell Line, EL4.IL-2*

Inhibition of signal transduction via the adenylate cyclase/cAMP pathway induces T-cell dysfunction which leads to a diminution in IL-2 gene transcription, suggesting that cannabinoid treatment decreases PMA/ionomycin-induced nuclear factor binding to the AP-1 proximal site of the IL- 2 promoter.