Agonist-Directed Trafficking of Response by Endocannabinoids Acting at CB2 Receptors
@article{Shoemaker2005AgonistDirectedTO, title={Agonist-Directed Trafficking of Response by Endocannabinoids Acting at CB2 Receptors}, author={Jennifer L. Shoemaker and Michael B Ruckle and Philip R. Mayeux and Paul L. Prather}, journal={Journal of Pharmacology and Experimental Therapeutics}, year={2005}, volume={315}, pages={828 - 838} }
This study examined the ability of the endocannabinoids 2-arachidonoyl glycerol (2-AG) and noladin ether as well as the synthetic cannabinoid CP-55,940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol] to regulate three intracellular effectors via CB2 receptors in transfected Chinese hamster ovary cells. Although the three agonists regulate all effectors with equivalent efficacy, the rank order of potencies differs depending on which effector is…
Figures and Tables from this paper
116 Citations
Differential Activation of Intracellular versus Plasmalemmal CB2 Cannabinoid Receptors
- BiologyBiochemistry
- 2014
Functional and morphological evidence is provided that CB2 receptors are localized at the endolysosomes, while their activation releases Ca2+ from inositol 1,4,5-trisphosphate-sensitive- and acidic-likeCa2+ stores.
Biochemistry, pharmacology and physiology of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand.
- Biology, ChemistryProgress in lipid research
- 2006
Functional Selectivity of CB2 Cannabinoid Receptor Ligands at a Canonical and Noncanonical Pathway
- ChemistryThe Journal of Pharmacology and Experimental Therapeutics
- 2016
Diverse CB2 receptor ligands at canonical (inhibition of adenylyl cyclase) and noncanonical (arrestin recruitment) pathways were screened, indicating a bias toward G-protein coupling for this class of compound.
Opposing Actions of Endocannabinoids on Cholangiocarcinoma Growth
- BiologyJournal of Biological Chemistry
- 2007
It is demonstrated that anandamide and ceramide treatment of cholangiocarcinoma cells recruited Fas and Fas ligand into the lipid rafts, subsequently activating death receptor pathways and suggesting that modulation of the endocannabinoid system may be a target for the development of possible therapeutic strategies for the treatment of this devastating cancer.
Mechanisms of osteoclastogenesis inhibition by a novel class of biphenyl-type cannabinoid CB(2) receptor inverse agonists.
- Biology, ChemistryChemistry & biology
- 2011
Cannabinoid receptor 2 and its agonists mediate hematopoiesis and hematopoietic stem and progenitor cell mobilization.
- Biology, MedicineBlood
- 2011
It is demonstrated that bone marrow stromal cells express endocannabinoids (anandamide and 2-arachidonylglycerol) and that CB₂/CB₁ agonist axis mediates repopulation of hematopoiesis and mobilization of HSPCs, and CB⁂ agonists may be therapeutically applied in clinical conditions, such as bone marrow transplantation.
Cannabinoid CB1 and CB2 Receptor-Mediated Arrestin Translocation: Species, Subtype, and Agonist-Dependence
- Biology, ChemistryFront. Pharmacol.
- 2019
A bioluminescence resonance energy transfer method is employed that does not require the use of tagged receptors and thereby allows comparisons of arrestin translocation between receptor types, as well as with cells lacking the receptor of interest – an important control.
Cannabinoid Receptor 2 Signalling Bias Elicited by 2,4,6-Trisubstituted 1,3,5-Triazines
- Biology, ChemistryFront. Pharmacol.
- 2018
A series of 2,4,6-trisubstituted 1,3,5-triazines with piperazinylalkyl or 1,2-diethoxyethane (PEG2) chains as CB2 agonists were designed and synthesised, all of which were predicted to be considerably more polar than typical cannabinoid ligands.
Alkylamides from Echinacea Are a New Class of Cannabinomimetics
- Chemistry, BiologyJournal of Biological Chemistry
- 2006
Overall, alkylamides, anandamide, and SR144528 potently inhibited lipopolysaccharide-induced inflammation in human whole blood and exerted modulatory effects on cytokine expression, but these effects are not exclusively related to CB2 binding.
References
SHOWING 1-10 OF 53 REFERENCES
The Endocannabinoid Noladin Ether Acts as a Full Agonist at Human CB2 Cannabinoid Receptors
- Biology, ChemistryJournal of Pharmacology and Experimental Therapeutics
- 2005
Surprisingly, in transfected CHO cells, NE exhibits a relatively high nanomolar affinity for CB2 receptors, comparable to that observed for the endocannabinoid 2-arachidonoyl glycerol (2-AG) (Ki = 1016 nM), which indicates that NE acts as a full agonist at human CB2 receptor and thus might have important physiological functions at peripheral cannabinoid receptors.
Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1.
- Biology, ChemistryThe Biochemical journal
- 1995
It is shown here that cannabinoid treatment induces both phosphorylation and activation of mitogen-activated protein (MAP) kinases, and that these effects are inhibited by SR 141716A, a selective CB1 antagonist.
Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus.
- Biology, PsychologyMolecular pharmacology
- 1998
Concentration-response curves to 5-HT2C agonists were fit well by a three-state model of receptor activation, suggesting that two active receptor states may be sufficient to explain pathway-dependent agonist efficacy.
Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors.
- Biology, ChemistryBiochemical pharmacology
- 1995
Unique allosteric regulation of 5-hydroxytryptamine receptor-mediated signal transduction by oleamide.
- BiologyProceedings of the National Academy of Sciences of the United States of America
- 1997
Results indicate that oleamide can modulate 5HT-mediated signal transduction at different subtypes of mammalian 5HT receptors and suggests that G protein-coupled neurotransmitter receptors may act like their iontropic counterparts (i.e., gamma-aminobutyric acid type A receptors) in that there may be several binding sites on the receptor that regulate functional activity with varying efficacies.
Evidence That 2-Arachidonoylglycerol but Not N-Palmitoylethanolamine or Anandamide Is the Physiological Ligand for the Cannabinoid CB2 Receptor
- Biology, ChemistryThe Journal of Biological Chemistry
- 2000
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.
Discrete activation of transduction pathways associated with acetylcholine m1 receptor by several muscarinic ligands.
- Biology, ChemistryEuropean journal of pharmacology
- 1994
Signaling pathway associated with stimulation of CB2 peripheral cannabinoid receptor. Involvement of both mitogen-activated protein kinase and induction of Krox-24 expression.
- BiologyEuropean journal of biochemistry
- 1996
Findings provide evidence for a functional role of the CB2 receptor in gene induction mediated by the MAP kinase network in time- and dose-dependent manners.
Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism.
- Biology, ChemistryMolecular pharmacology
- 2004
2-AG activation of CB(2) receptors may contribute to the proliferative response of microglial cells, as occurs in neurodegenerative disorders.
2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor
- Chemistry, BiologyProceedings of the National Academy of Sciences of the United States of America
- 2001
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.