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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

ROB LANE ROB.LANE@NOTTINGHAM.AC.UK
Associate Professor

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
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 http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=19665453&retmode=ref&cmd=prlinks
Publisher URL https://www.sciencedirect.com/science/article/abs/pii/S0006295209006777