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The activity of the Striatal‐enriched protein tyrosine phosphatase in neuronal cells is modulated by adenosine A 2A receptor
Author(s) -
Mallozzi Cinzia,
Pepponi Rita,
Visentin Sergio,
Chiodi Valentina,
Lombroso Paul J.,
Bader Michael,
Popoli Patrizia,
Domenici Maria Rosaria
Publication year - 2020
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14866
Subject(s) - protein tyrosine phosphatase , phosphatase , adenosine a2a receptor , agonist , medicine , receptor , striatum , endocrinology , tyrosine , biology , adenosine , biochemistry , antagonist , tyrosine phosphorylation , chemistry , phosphorylation , pharmacology , adenosine receptor , dopamine
We recently demonstrated that a tonic activation of adenosine A 2A receptors (A 2A Rs) is required for cocaine‐induced synaptic depression and increase in the activity of STriatal‐Enriched protein tyrosine Phosphatase (STEP). In this study, we elaborated on the relationship between A 2A 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‐expressing the neuronal A 2A R (NSEA 2A ) with respect to wild‐type (WT) rats. Moreover the selective A 2A R agonist 4‐[2‐[[6‐Amino‐9‐( N ‐ethyl‐β‐ d ‐ribofuranuronamidosyl)‐9 H ‐purin‐2‐yl]amino]ethyl]benzenepropanoic acid hydrochloride up‐regulates PTPs and STEP activities in WT but not in NSEA 2A rats, while the selective A 2A R antagonist 4‐(−2‐[7‐amino‐2‐{2‐furyl}{1,2,4}triazolo{2,3‐a} {1,3,5}triazin‐5‐yl‐amino]ethyl)phenol restores the tyrosine phosphatase activities in NSEA 2A , 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 2A rats. A 2A Rs modulate STEP activity also in the SH‐SY5Y neuroblastoma cell line, where a calcium‐dependent calcineurin/PP1 pathway was found to play a major role. In summary, the present study identified a novel interaction between A 2A 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 2A Rs are considered a promising target for the development of therapeutic strategies for different diseases of the central nervous system.Read the Editorial Highlight for this article on page 270