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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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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
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CASANOVAS MONTASELL, Mireia, REYES RESINA, Irene, LILLO, Alejandro, LILLO, Jaume, LÓPEZ-ARNAU, Raúl, CAMARASA GARCÍA, Jordi, ESCUBEDO RAFA, Elena, NAVARRO BRUGAL, Gemma, FRANCO FERNÁNDEZ, Rafael. Methamphetamine Blocks Adenosine A2A Receptor Activation via Sigma 1 and Cannabinoid CB1 Receptors. _International Journal of Molecular Sciences_. 2021. [consulta: 21 de gener de 2026]. ISSN: 1661-6596. [Disponible a: https://hdl.handle.net/2445/176634]