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Title: | Methamphetamine Blocks Adenosine A2A Receptor Activation via Sigma 1 and Cannabinoid CB1 Receptors |
Author: | 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 |
Keywords: | Malalties neurodegeneratives Drogues Receptors colinèrgics Neurodegenerative Diseases Drugs of abuse Acetylcholine receptors |
Issue Date: | 9-Mar-2021 |
Publisher: | MDPI |
Abstract: | 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 |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/ijms22052743 |
It is part of: | International Journal of Molecular Sciences, 2021 |
URI: | http://hdl.handle.net/2445/176634 |
Related resource: | https://doi.org/10.3390/ijms22052743 |
ISSN: | 1661-6596 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Fisiologia) Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
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