Sánchez Fernández, NuriaGómez Acero, LauraSarasola, Laura I.Argerich Bergadà, JosepChevigné, AndyJacobson, Kenneth A.Ciruela Alférez, FranciscoFernández Dueñas, VíctorAso Pérez, Ester2025-03-062025-03-062024-10-010924-2708https://hdl.handle.net/2445/219512Objectives: 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 NanoBiT™ 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.5 p.application/pdfengcc by (c) Sánchez Fernández, Nuria et al., 2024https://creativecommons.org/licenses/by/4.0/CànnabisAdenosinaCèl·lules epitelialsCannabisAdenosineEpithelial cellsinfo:eu-repo/semantics/article7396712025-03-06info:eu-repo/semantics/openAccess37605951