{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T14:00:45Z","timestamp":1774447245409,"version":"3.50.1"},"reference-count":82,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T00:00:00Z","timestamp":1570665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>We recently demonstrated that a tonic activation of adenosine A<jats:sub>2A<\/jats:sub> receptors (A<jats:sub>2A<\/jats:sub>Rs) is required for cocaine\u2010induced synaptic depression and increase in the activity of STriatal\u2010Enriched protein tyrosine Phosphatase (STEP). In this study, we elaborated on the relationship between A<jats:sub>2A<\/jats:sub>R and STEP using genetic, pharmacological, and cellular tools. We found that the activities of protein tyrosine phosphatases (PTPs), and in particular of STEP, are significantly increased in the striatum and hippocampus of a transgenic rat strain over\u2010expressing the neuronal A<jats:sub>2A<\/jats:sub>R (NSEA<jats:sub>2A<\/jats:sub>) with respect to wild\u2010type (WT) rats. Moreover the selective A<jats:sub>2A<\/jats:sub>R agonist 4\u2010[2\u2010[[6\u2010Amino\u20109\u2010(<jats:italic>N<\/jats:italic>\u2010ethyl\u2010\u03b2\u2010<jats:sc>d<\/jats:sc>\u2010ribofuranuronamidosyl)\u20109<jats:italic>H<\/jats:italic>\u2010purin\u20102\u2010yl]amino]ethyl]benzenepropanoic acid hydrochloride up\u2010regulates PTPs and STEP activities in WT but not in NSEA<jats:sub>2A<\/jats:sub> rats, while the selective A<jats:sub>2A<\/jats:sub>R antagonist 4\u2010(\u22122\u2010[7\u2010amino\u20102\u2010{2\u2010furyl}{1,2,4}triazolo{2,3\u2010a} {1,3,5}triazin\u20105\u2010yl\u2010amino]ethyl)phenol restores the tyrosine phosphatase activities in NSEA<jats:sub>2A<\/jats:sub>, having no effects in WT rats. In addition, while cocaine induced the activation of PTP and STEP in WT rats, it failed to increase phosphatase activity in NSEA<jats:sub>2A<\/jats:sub> rats. A<jats:sub>2A<\/jats:sub>Rs modulate STEP activity also in the SH\u2010SY5Y neuroblastoma cell line, where a calcium\u2010dependent calcineurin\/PP1 pathway was found to play a major role. In summary, the present study identified a novel interaction between A<jats:sub>2A<\/jats:sub>R and STEP that could have important clinical implications, since STEP has emerged as key regulator of signaling pathways involved in neurodegenerative and neuropsychiatric diseases and A<jats:sub>2A<\/jats:sub>Rs are considered a promising target for the development of therapeutic strategies for different diseases of the central nervous system.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14866-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p><jats:bold>Read the Editorial Highlight for this article on page <\/jats:bold> <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1111\/jnc.14901\">270<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14866","type":"journal-article","created":{"date-parts":[[2019,9,14]],"date-time":"2019-09-14T13:49:15Z","timestamp":1568468955000},"page":"284-298","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The activity of the Striatal\u2010enriched protein tyrosine phosphatase in neuronal cells is modulated by adenosine A<sub>2A<\/sub> receptor"],"prefix":"10.1111","volume":"152","author":[{"given":"Cinzia","family":"Mallozzi","sequence":"first","affiliation":[{"name":"Department of Neuroscience Istituto Superiore di Sanit\u00e0 Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Pepponi","sequence":"additional","affiliation":[{"name":"National Centre for Drug Research and Evaluation Istituto Superiore di Sanit\u00e0 Rome 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