A2A adenosine receptor function in patients with vasovagal syncope

Abstract

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.

Spare Adenosine A2a Receptors Are Associated with Positive Exercise Stress Test in Coronary Artery Disease

“…While the K D for A 2A R of the agonist used here to mimic adenosine was similar in patients and controls, the EC 50 value (related to the biological effect triggered by the Spare A 2A R was first observed in guinea pig cardiac tissue using an irreversible A 2A R antagonist to block response to various agonists (13). Here, we used an agonist-like monoclonal antibody and provided further evidence for the presence of spare A 2A R on the surface of human mononuclear cells in relation to cardiac dysfunction, spare A 2A R having already been observed in a context of neurocardiogenic syncope, but not in healthy subjects (14,15,18).…”

“…Seventeen control patients (10 men and (14,15), with only the kappa light chain (25 kDa) being stained here using specific peroxidase-labeled antibodies and chemiluminescent substrate. The staining intensity was measured using densitometry analysis and expressed as AU (that is, the ratio of pixels generated by the light chain band to pixels generated by the background signal).…”

“…The procedure has been described previously (14,15). In brief, blood samples Western blot analysis of cell lysates and probing with the anti-A 2A R monoclonal antibody Adonis prior to densitometry analysis of the 45-kDa band.…”

“…The presence of spare A 2A R is evidenced when activation of only a weak fraction of A 2A R (evaluated using the K D variable) results in maximal cAMP production (evaluated using the EC 50 variable), and hence in maximal coronary vasodilation (13)(14)(15). Thus, the presence of spare A 2A R allows for rapid, transient responses that are sensitive to low agonist concentrations.…”

Specific Pharmacological Profile of A 2A Adenosine Receptor Predicts Reduced Fractional Flow Reserve in Patients With Suspected Coronary Artery Disease

“…As described above, PBMC (0.25×10 6 /test) previously incubated with increasing concentrations of Adonis were solubilized by sonication in lysis buffer containing 5% mercaptoethanol before sodium dodecyl sulfate polyacrylamide (12%) gel electrophoresis using 60×90 mm, 1.5‐mm thick minigel (Biorad, Hercules, CA), transfer onto a 0.45 μmol/L polyvinylidene difluoride membrane and saturation with non‐fat dried milk. The reducing conditions led to the dissociation of Adonis into its heavy and light chains 5, 17. Only the blotted kappa light chain (25 kDa) was visualized using an image station (Kodack Rochester, NY) after incubation of the membrane with peroxidase‐labeled anti‐mouse μ‐chain antibodies and a chemiluminescent substrate.…”