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2025-10

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cc-by (c) Raïch, Iu et al., 2025
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/228919

Cannabidiol releases CB1R from A2AR repression in ischemic stroke.

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Recurs relacionat

https://doi.org/10.1016/j.nbd.2025.107131

Resum

Cannabidiol (CBD) is a phytocannabinoid with potential in one of the most prevalent syndromes occurring at birth, the hypoxia of the neonate. CBD targets a variety of proteins, adenosine A2AR and cannabinoid CB1R receptors included. These two receptors may interact to form heteromers (A2AR-CB1R Hets) that are also a target of CBD. Thus, we aimed to assess whether the expression and function of A2AR–CB1R-Hets is affected by CBD in animal models of hypoxia of the neonate and in glucose- and oxygen deprived (GOD) neurons and microglial cells. Results indicated that the formation of A2AR-CB1R heteromers increased A2AR affinity for its selective agonist CGS21680. Moreover, resonance energy transfer assays showed that CBD and cannabigerol (CBG) affected the structure of the heteromer. Regarding functionallity, CBD partially bloked A2AR induced signalling in transfected HEK-293 T cells, while it recovered CB1R signalling in glucose/oxygen-deprived neurons and microglial cells. The expression of A2AR-CB1R Hets increased in GOD neurons and microglial cells. This increase was counteracted with a pre-treatment with CBD and CBG. Importantly, in brain sections of a hypoxia/ischemia animal model, administration of CBD led to a significant reduction in the expression of A2AR-CB1R Hets. In conclusion, CBD effects in the hypoxia of the neonate can be mediated by A2AR-CB1R complex. CBD partially blocks A2AR signalling while potentiates the neuroprotective effect of CB1R in hypoxic-ischemic conditions.

Matèries

Malalties neonatals, Isquèmia, Cànnabis

Matèries (anglès)

Neonatal diseases, Ischemia, Cannabis

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Col·leccions

Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

Citació

RAÏCH, Iu, et al. Cannabidiol releases CB1R from A2AR repression in ischemic stroke. Neurobiology of Disease. 2025. Vol. 216. ISSN 0969-9961. [consulted: 23 of May of 2026]. Available at: https://hdl.handle.net/2445/228919

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