The Endocannabinoid Noladin Ether Acts as a Full Agonist at Human CB2 Cannabinoid Receptors

@article{Shoemaker2005TheEN,
  title={The Endocannabinoid Noladin Ether Acts as a Full Agonist at Human CB2 Cannabinoid Receptors},
  author={Jennifer L. Shoemaker and Biny K. Joseph and Michael B. Ruckle and Philip R. Mayeux and Paul L. Prather},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2005},
  volume={314},
  pages={868 - 875}
}
Noladin ether (NE) is a putative endogenously occurring cannabinoid demonstrating agonist activity at CB1 receptors. Because of reported selective affinity for CB1 receptors, the pharmacological actions of NE at CB2 receptors have not been examined. Therefore, the purpose of this study was to characterize the binding and functional properties of NE at human CB2 receptors stably expressed in Chinese hamster ovary (CHO) cells as well as in HL-60 cells, which express CB2 receptors endogenously… 

Figures and Tables from this paper

Resorcinol-sn-glycerol derivatives: novel 2-arachidonoylglycerol mimetics endowed with high affinity and selectivity for cannabinoid type 1 receptor.

The cannabinoid receptor binding properties, the CB1 functional activity, and the stability to plasma esterases of a novel series of compounds characterized by the conversion of the amide head into the glycerol-ester or glycerl-ether head, typical of 2-AG or the "putative" endocannabinoid 2-AGE, respectively are explored.

Cannabichromene is a cannabinoid CB2 receptor agonist

Cannabichromene is a selective CB2 receptor agonist displaying higher efficacy than THC in hyperpolarising AtT20 cells and may contribute to the potential therapeutic effectiveness of some cannabis preparations, potentially through CB2-mediated modulation of inflammation.

Agonist-Directed Trafficking of Response by Endocannabinoids Acting at CB2 Receptors

Endocannabinoid agonists distinctly bind to CB2 receptors and display different rank order of potencies and fractional receptor occupancies for regulation of intracellular effectors, providing direct evidence for agonist-directed trafficking of response by endocannabinoids acting atCB2 receptors.

The endocannabinoid system.

Thirty years ago, the discovery of a cannabinoid (CB) receptor that interacts with the psychoactive compound in Cannabis led to the identification of anandamide, an endogenous receptor ligand or endocannabinoid, which enabled the development of the ECS.

DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL SELECTIVE CANNABINOID RECEPTOR 2 (CB2) LIGANDS WITH THERAPEUTIC POTENTIALS

Toxic studies showed that inverse agonism is essential for the OCL inhibition effects while anti-MM experiments showed that CB2 agonists are more effective than inverse agonists, and several novel compounds were discovered with high potency and selectivity.

Novel fenofibrate derivatives as cannabinoid receptor ligands

This project sought to develop novel ligands for the cannabinoid receptors that retain activity at PPARα with a series of amide derivatives of fenofibrate synthesised, and pharmacological testing revealed that the piperidinyl and morpholino derivatives had agonist activity and a higher affinity for the cannabinoids receptors than fen ofibrate, however these derivatives failed to bind and activate PPAR α.
...

References

SHOWING 1-10 OF 43 REFERENCES

New perspectives in the studies on endocannabinoid and cannabis: 2-arachidonoylglycerol as a possible novel mediator of inflammation.

2-arachidonoylglycerol plays essential roles in the stimulation of various inflammatory reactions in vivo and is found to induce acute inflammation following treatment with 12-O-tetradecanoylphorbol 13-acetate.

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.

2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor

Two types of endogenous cannabinoid-receptor agonists have been identified thus far and an example of a third, ether-type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether), isolated from porcine brain is reported.

Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors.

Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor.

Virodhamine produced hypothermia in the mouse and acted as an antagonist in the presence of anandamide both in vivo and in vitro, adding a new form of regulation to the endocannabinoid system.

The endogenous cannabinoid system and its role in nociceptive behavior.

Recent genetic, behavioral, and pharmacological studies support a role for endocannabinoids in modulating behavioral responses to acute, inflammatory, and neuropathic pain stimuli.

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.

The cannabinoid system and immune modulation

It appears the immunocannabinoid system is involved in regulating the brain‐immune axis and might be exploited in future therapies for chronic diseases and immune deficiency.

International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors

It is considered premature to rename cannabinoid receptors after an endogenous agonist as is recommended by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification, because pharmacological evidence for the existence of additional types of cannabinoid receptor is emerging and other kinds of supporting evidence are still lacking.