A2A adenosine receptor function in patients with vasovagal syncope

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Abstract
Adenosine is a possible mediator in vasovagal syncope (VVS) via the activation of its receptors. High expression of adenosine A2A receptors (A2AR) has been reported in VVS. The function of these over-expressed receptors in this population has never been evaluated. We used Adonis, a specific-made antibody with A2AR agonist properties, to evaluate binding parameters (i.e. dissociation constant KD) and cAMP production (i.e. EC50) by peripheral blood mononuclear cells of 16 VVS patients. Eight healthy volunteers served as controls. A2AR expression was higher in patients than controls; mean: 11.5 ± 1.2 vs. 7.7 ± 0.8 AU, P = 0.04. Also, KD values were higher in patients than controls: 2.1 ± 0.02 × 10−7 vs. 5 ± 1 × 10−8 M, P < 0.01 In controls, KD values were lower than EC50 (5 ± 1.7 × 10−8 vs. 2.8 ± 0.4 10−7 M, P < 0.01), but in patients, KD values did not differ from EC50: 2. ± 0.2 × 10−7 vs. 2.5 ± 0.4 × 10−7 M, P > 0.05. However, four patients had lower EC50 (3.5 ± 0.3 × 10−8 M) than KD (2.9 ± 1.2 × 10−7 M; KD/EC50 = 9.6), suggesting the presence of spare receptors. The function of A2AR of patients with VVS was preserved since their stimulation by Adonis led to cAMP production with an EC50 comparable with those in controls. However, their affinity was lower than those of controls. Our results suggest that A2AR are implicated in the physiopathology of VVS.

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