Binding and Signaling Studies Disclose a Potential Allosteric Site for Cannabidiol in Cannabinoid CB2 Receptors

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RECERCAT Home > Universitat de Barcelona > Bioquímica i Biomedicina Molecular > Articles publicats en revistes (Bioquímica i Biomedicina Molecular) > View document

To access the full text documents, please follow this link: http://hdl.handle.net/2445/122632

dc.contributor	Universitat de Barcelona
dc.contributor.author	Martínez-Pinilla, Eva
dc.contributor.author	Varani, Katia
dc.contributor.author	Reyes-Resina, Irene
dc.contributor.author	Angelats, Edgar
dc.contributor.author	Vincenzi, Fabrizio
dc.contributor.author	Ferreiro-Vera, Carlos
dc.contributor.author	Oyarzabal, Julen
dc.contributor.author	Canela Campos, Enric I.
dc.contributor.author	Lanciego, José Luis
dc.contributor.author	Nadal, Xavier
dc.contributor.author	Navarro Brugal, Gemma
dc.contributor.author	Borea, Pier Andrea
dc.contributor.author	Franco Fernández, Rafael
dc.date	2018-05-29T11:24:29Z
dc.date	2018-05-29T11:24:29Z
dc.date	2017-10-23
dc.date	2018-05-29T11:24:29Z
dc.identifier.citation	1663-9812
dc.identifier.citation	674872
dc.identifier.uri	http://hdl.handle.net/2445/122632
dc.description.abstract	The mechanism of action of cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa L., is not completely understood. First assumed that the compound was acting via cannabinoid CB2 receptors (CB(2)Rs) it is now suggested that it interacts with non-cannabinoid G-protein-coupled receptors (GPCRs); however, CBD does not bind with high affinity to the orthosteric site of any GPCR. To search for alternative explanations, we tested CBD as a potential allosteric ligand of CB2R. Radioligand and non-radioactive homogeneous binding, intracellular cAMP determination and ERK1/2 phosphorylation assays were undertaken in heterologous systems expressing the human version of CB2R. Using membrane preparations from CB2R-expressing HEK-293T (human embryonic kidney 293T) cells, we confirmed that CBD does not bind with high affinity to the orthosteric site of the human CB2R where the synthetic cannabinoid, [H-3]-WIN 55,212-2, binds. CBD was, however, able to produce minor but consistent reduction in the homogeneous binding assays in living cells using the fluorophore-conjugated CB2R-selective compound, CM-157. The effect on binding to CB2R-expressing living cells was different to that exerted by the orthosteric antagonist, SR144528, which decreased the maximum binding without changing the K-D. CBD at nanomolar concentrations was also able to significantly reduce the effect of the selective CB2R agonist, JWH133, on forskolin-induced intracellular cAMP levels and on activation of the MAP kinase pathway. These results may help to understand CBD mode of action and may serve to revisit its therapeutic possibilities.
dc.format	10 p.
dc.format	application/pdf
dc.language.iso	eng
dc.publisher	Frontiers Media
dc.relation	Reproducció del document publicat a: https://doi.org/10.3389/fphar.2017.00744
dc.relation	Frontiers in Pharmacology, 2017, vol. 8
dc.relation	https://doi.org/10.3389/fphar.2017.00744
dc.rights	cc-by (c) Martinez-Pinilla, Eva et al., 2017
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	http://creativecommons.org/licenses/by/3.0/es
dc.subject	Receptors cel·lulars
dc.subject	Proteïnes G
dc.subject	Cell receptors
dc.subject	G Proteins
dc.title	Binding and Signaling Studies Disclose a Potential Allosteric Site for Cannabidiol in Cannabinoid CB2 Receptors
dc.type	info:eu-repo/semantics/article
dc.type	info:eu-repo/semantics/publishedVersion

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