Dr ROB LANE ROB.LANE@NOTTINGHAM.AC.UK
ASSOCIATE PROFESSOR
The endocannabinoid 2-arachidonylglycerol is a negative allosteric modulator of the human A3 adenosine receptor
Lane, J Robert; Beukers, Margot W; Mulder-Krieger, Thea; IJzerman, Ad P
Authors
Margot W Beukers
Thea Mulder-Krieger
Ad P IJzerman
Abstract
Studies of endogenous cannabinoid agonists, such as 2-arachidonylglycerol (2-AG), have revealed their potential to exert modulatory actions on other receptor systems in addition to their ability to activate cannabinoid receptors. This study investigated the effect of cannabinoid ligands on the human adenosine A(3) (hA(3)R) receptor. The endocannabinoid 2-AG was able to inhibit agonist ([125I]N(6)-(4-amino-3-iodobenzyl) adenosine-5'-(N-methyluronamide)--[125I] AB MECA) binding at the hA(3)R. This inhibition occurred over a narrow range of ligand concentration and was characterized by high Hill coefficients suggesting a non-competitive interaction. Furthermore, in the presence of 2-AG, the rate of [125I] AB MECA dissociation was increased, consistent with an action as a negative allosteric modulator of the hA(3)R. Moreover, by measuring intracellular cAMP levels, we demonstrate that 2-AG decreases both the potency of an agonist at the hA(3)R and the basal signalling of this receptor. Since the hA(3)R has been shown to be expressed in astrocytes and microglia, these findings may be particularly relevant in certain pathological states such as cerebral ischemia where levels of 2-AG and anandamide are raised.
Citation
Lane, J. R., Beukers, M. W., Mulder-Krieger, T., & IJzerman, A. P. (2010). The endocannabinoid 2-arachidonylglycerol is a negative allosteric modulator of the human A3 adenosine receptor. Biochemical Pharmacology, 79(1), 48-56. https://doi.org/10.1016/j.bcp.2009.07.024
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 31, 2009 |
Online Publication Date | Aug 7, 2009 |
Publication Date | Jan 1, 2010 |
Deposit Date | Apr 22, 2020 |
Journal | Biochemical Pharmacology |
Print ISSN | 0006-2952 |
Electronic ISSN | 1873-2968 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 79 |
Issue | 1 |
Pages | 48-56 |
DOI | https://doi.org/10.1016/j.bcp.2009.07.024 |
Public URL | https://nottingham-repository.worktribe.com/output/1339570 |
Publisher URL | https://www.sciencedirect.com/science/article/abs/pii/S0006295209006777 |
You might also like
Systematic assessment of chemokine signaling at chemokine receptors ccr4, ccr7 and ccr10
(2021)
Journal Article
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2025
Advanced Search