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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

Citació

Col·leccions

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: 17 of August of 2026]. Available at: https://hdl.handle.net/2445/176634

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