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2021-03-09

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cc-by (c) Casanovas Montasell, Mireia et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/176634

Methamphetamine Blocks Adenosine A2A Receptor Activation via Sigma 1 and Cannabinoid CB1 Receptors

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Recurs relacionat

https://doi.org/10.3390/ijms22052743

Resum

Methamphetamine is, worldwide, one of the most consumed drugs of abuse. One important side effect is neurodegeneration leading to a decrease in life expectancy. The aim of this paper was to check whether the drug affects one of the receptors involved in neurodegeneration/neuroprotection events, namely the adenosine A2A receptor (A2AR). First, we noticed that methamphetamine does not affect A2A functionality if the receptor is expressed in a heterologous system. However, A2AR becomes sensitive to the drug upon complexes formation with the cannabinoid CB1 receptor (CB1R) and the sigma 1 receptor (σ1R). Signaling via both adenosine A2AR and cannabinoid CB1R was affected by methamphetamine in cells co-expressing the two receptors. In striatal primary cultures, the A2AR-CB1R heteromer complex was detected and methamphetamine not only altered its expression but completely blocked the A2AR- and the CB1R-mediated activation of the mitogen activated protein kinase (MAPK) pathway. In conclusion, methamphetamine, with the participation of σ1R, alters the expression and function of two interacting receptors, A2AR, which is a therapeutic target for neuroprotection, and CB1R, which is the most abundant G protein-coupled receptor (GPCR) in the brain. Keywords: G protein-coupled receptor GPCR, striatal neurons, heteromer, drug of abuse, neuroprotection

Matèries

Malalties neurodegeneratives, Drogues, Receptors colinèrgics

Matèries (anglès)

Neurodegenerative Diseases, Drugs of abuse, Acetylcholine receptors

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Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

Citació

CASANOVAS MONTASELL, Mireia, et al. Methamphetamine Blocks Adenosine A2A Receptor Activation via Sigma 1 and Cannabinoid CB1 Receptors. International Journal of Molecular Sciences. 2021. ISSN 1661-6596. [consulted: 23 of June of 2026]. Available at: https://hdl.handle.net/2445/176634

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