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Cannabidiol at Nanomolar Concentrations Negatively Affects Signaling through the Adenosine A_2A Receptor.

ABSTRACT: Cannabidiol (CBD) is a phytocannabinoid with potential as a therapy for a variety of diseases. CBD may act via cannabinoid receptors but also via other G-protein-coupled receptors (GPCRs), including the adenosine A_2A receptor. Homogenous binding and signaling assays in Chinese hamster ovary (CHO) cells expressing the human version of the A_2A receptor were performed to address the effect of CBD on receptor functionality. CBD was not able to compete for the binding of a SCH 442416 derivative labeled with a red emitting fluorescent probe that is a selective antagonist that binds to the orthosteric site of the receptor. However, CBD reduced the effect of the selective A_2A receptor agonist, CGS 21680, on G_s-coupling and on the activation of the mitogen activated kinase signaling pathway. It is suggested that CBD is a negative allosteric modulator of the A_2A receptor.

SUBMITTER: Raich I

PROVIDER: S-EPMC10744210 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Cannabidiol at Nanomolar Concentrations Negatively Affects Signaling through the Adenosine A2A Receptor.

Raïch Iu I Lillo Jaume J Ferreiro-Vera Carlos C Sánchez de Medina Verónica V Navarro Gemma G Franco Rafael R

International journal of molecular sciences 20231215 24

Cannabidiol (CBD) is a phytocannabinoid with potential as a therapy for a variety of diseases. CBD may act via cannabinoid receptors but also via other G-protein-coupled receptors (GPCRs), including the adenosine A2A receptor. Homogenous binding and signaling assays in Chinese hamster ovary (CHO) cells expressing the human version of the A2A receptor were performed to address the effect of CBD on receptor functionality. CBD was not able to compete for the binding of a SCH 4 ...[more]

PMID: 38139329

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