title: A2A adenosine receptors are up-regulated in lymphocytes from amyotrophic lateral sclerosis patients.
abstract: Adenosine, a purine nucleoside interacting with A1, A2A, A2B and A3 adenosine receptors (ARs), is a potent endogenous modulator of inflammatory and neuronal processes involved in the pathophysiology of several neurodegenerative diseases. In the present study, ARs were investigated in lymphocytes from patients with amyotrophic lateral sclerosis (ALS) and compared with age-matched healthy subjects. In ALS patients A2AARs were analysed by using RT-PCR, Western blotting and saturation binding experiments. The effect of A2AAR stimulation on cyclic AMP levels was evaluated in lymphocytes from ALS patients and healthy subjects. An up-regulation of A2AARs was observed in ALS patients with respect to healthy subjects while A1, A2B and A3AR affinity and density did not change. In ALS patients, the A2AAR density values correlated with the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Furthermore, the stimulation of A2AARs mediated a significant increase in cyclic AMP levels in lymphocytes from ALS patients, with a higher potency than in lymphocytes from healthy subjects. In conclusion, the positive correlation between A2AAR density and ALSFRS-R scores could indicate a possible protective effect of this receptor subtype, representing an interesting starting point for the study of alternative therapeutic approaches for ALS based on A2AAR modulation.
authors.affiliation: Department of Medical Sciences, Pharmacology Section, University of Ferrara, via Fossato di Mortara 17-19, Ferrara, Italy
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vincenzi
authors.forename: Carmen
authors.initials: C
authors.lastname: Corciulo
authors.forename: Martina
authors.initials: M
authors.lastname: Targa
authors.forename: Ilaria
authors.initials: I
authors.lastname: Casetta
authors.forename: Mauro
authors.initials: M
authors.lastname: Gentile
authors.forename: Enrico
authors.initials: E
authors.lastname: Granieri
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
authors.forename: Patrizia
authors.initials: P
authors.lastname: Popoli
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D058908:Adenosine A2 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D000242:Cyclic AMP