TY - JOUR
T1 - Cannabidiol negatively modulates adenosine A2A receptor functioning in living cells
AU - Sánchez-Fernández, Nuria
AU - Gómez-Acero, Laura
AU - Sarasola, Laura I.
AU - Argerich, Josep
AU - Chevigné, Andy
AU - Jacobson, Kenneth A.
AU - Ciruela, Francisco
AU - Fernández-Dueñas, Víctor
AU - Aso, Ester
N1 - Financial support
This study was supported by Ministerio de Ciencia, Innovación y Universidades–Agencia Estatal de Investigación-FEDER funds/European Regional Development Fund – “a way to build Europe” grant RTI2018-097773-A-I00 to EA and PID2020-118511RB-I00 to FC. Founded by MCIN/AEI /10.13039/501100011033 “ESF Investing in your future” grant PRE2018–084480 to JA, grant PRE2019-088153 to NSF and grant FPU19/03142 to LGA. Also supported by "Acció instrumental de formació de científics i tecnòlegs" (SLT017/20/000114) of the Departament de Salut de la Generalitat de Catalunya to LIS. The study was also supported by the Luxembourg Institute of Health (LIH), Luxembourg National Research Fund (INTER/FNRS grants 20/15084569 to AC) and the National Institute of Diabetes and Digestive and Kidney Diseases NIDDK Intramural Research Program (ZIADK031117 to KAJ).
PY - 2024/10
Y1 - 2024/10
N2 - Objectives: Cannabidiol (CBD) is a phytocannabinoid with great potential in clinical applications. The mechanism(s) of action of CBD require further investigation. Previous studies suggested that adenosine A2A receptors (A2ARs) could play a role in CBD-induced effects. Here, we evaluated the ability of CBD to modify the function of A2AR. Methods: We used HEK-293T cells transfected with the cDNA encoding the human A2AR and Gαs protein, both modified to perform bioluminescence-based assays. We first assessed the effect of CBD on A2AR-ligand binding using an A2AR NanoLuciferase sensor. Next, we evaluated whether CBD modified A2AR coupling to mini-Gαs proteins using the NanoBiTTM assay. Finally, we further assessed CBD effects on A2AR intrinsic activity by recording agonist-induced cAMP accumulation. Results: CBD did not bind orthosterically to A2AR but reduced the coupling of A2AR to Gαs protein and the subsequent generation of cAMP. Conclusion: CBD negatively modulates A2AR functioning.
AB - Objectives: Cannabidiol (CBD) is a phytocannabinoid with great potential in clinical applications. The mechanism(s) of action of CBD require further investigation. Previous studies suggested that adenosine A2A receptors (A2ARs) could play a role in CBD-induced effects. Here, we evaluated the ability of CBD to modify the function of A2AR. Methods: We used HEK-293T cells transfected with the cDNA encoding the human A2AR and Gαs protein, both modified to perform bioluminescence-based assays. We first assessed the effect of CBD on A2AR-ligand binding using an A2AR NanoLuciferase sensor. Next, we evaluated whether CBD modified A2AR coupling to mini-Gαs proteins using the NanoBiTTM assay. Finally, we further assessed CBD effects on A2AR intrinsic activity by recording agonist-induced cAMP accumulation. Results: CBD did not bind orthosterically to A2AR but reduced the coupling of A2AR to Gαs protein and the subsequent generation of cAMP. Conclusion: CBD negatively modulates A2AR functioning.
KW - adenosine 2A receptor
KW - cannabidiol
KW - competitive binding
KW - cyclic AMP
KW - luminescence-based assays
KW - negative allosteric regulation
UR - http://www.scopus.com/inward/record.url?scp=85170848320&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/37605951
U2 - 10.1017/neu.2023.30
DO - 10.1017/neu.2023.30
M3 - Article
C2 - 37605951
SN - 0924-2708
VL - 36
SP - 320
EP - 324
JO - Acta Neuropsychiatrica
JF - Acta Neuropsychiatrica
IS - 5
ER -