A_2A adenosine receptors are up-regulated in lymphocytes from amyotrophic lateral sclerosis patients

Abstract

Adenosine, a purine nucleoside interacting with A₁, A_2A, A_2B 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 A_2AARs were analysed by using RT-PCR, Western blotting and saturation binding experiments. The effect of A_2AAR stimulation on cyclic AMP levels was evaluated in lymphocytes from ALS patients and healthy subjects.

An up-regulation of A_2AARs was observed in ALS patients with respect to healthy subjects while A₁, A_2B and A₃AR affinity and density did not change. In ALS patients, the A_2AAR density values correlated with the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Furthermore, the stimulation of A_2AARs 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 A_2AAR 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 A_2AAR modulation.

Key words::

• Adenosine receptors
• ALS patients
• human lymphocytes
• saturation binding experiments
• cyclic AMP assays

Declaration of interest: The authors report no conflict of interest. The authors are responsible for the content and writing of the paper.