title: Striatal adenosine A2A receptor expression is controlled by S-adenosyl-L-methionine-mediated methylation.
abstract: Adenosine A2A receptor (A2AR) is a G protein-coupled receptor enriched in the striatum for which an increased expression has been demonstrated in certain neurological diseases. Interestingly, previous in vitro studies demonstrated that A2AR expression levels are reduced after treatment with S-adenosyl-L-methionine (SAM), a methyl donor molecule involved in the methylation of important biological structures such as DNA, proteins, and lipids. However, the in vivo effects of SAM treatment on A2AR expression are still obscure. Here, we demonstrated that 2 weeks of SAM treatment produced a significant reduction in the rat striatal A2AR messenger RNA (mRNA) and protein content as well as A2AR-mediated signaling. Furthermore, when the content of 5-methylcytosine levels in the 5'UTR region of ADORA2A was analyzed, this was significantly increased in the striatum of SAM-treated animals; thus, an unambiguous correlation between SAM-mediated methylation and striatal A2AR expression could be established. Overall, we concluded that striatal A2AR functionality can be controlled by SAM treatment, an issue that might be relevant for the management of these neurological conditions that course with increased A2AR expression.
authors.affiliation: Institute of Neuropathology, Bellvitge Biomedical Research Institute (IDIBELL), Bellvitge University Hospital-ICS, Av. Gran Via de L'Hospitalet 199, L'Hospitalet de Llobregat, 08908, Spain.
authors.forename: Izaskun
authors.initials: I
authors.lastname: Villar-Menéndez
authors.forename: Fabiana
authors.initials: F
authors.lastname: Nuñez
authors.forename: Sara
authors.initials: S
authors.lastname: Díaz-Sánchez
authors.forename: José Luis
authors.initials: JL
authors.lastname: Albasanz
authors.forename: Jaume
authors.initials: J
authors.lastname: Taura
authors.forename: Víctor
authors.initials: V
authors.lastname: Fernández-Dueñas
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.forename: Mairena
authors.initials: M
authors.lastname: Martín
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.forename: Marta
authors.initials: M
authors.lastname: Barrachina
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D008745:Methylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000096:biosynthesis*; D012436:S-Adenosylmethionine / Q000494:pharmacology*
chemical_list: D043705:Receptor, Adenosine A2A; D012436:S-Adenosylmethionine