Some ligand-receptor couples involve spare receptors, which are apparent when a maximal response is achieved with only a small fraction of the receptor population occupied. This situation favours cross-reactions with low-affinity ligands, which may be detrimental for cell signaling. In the case of the adenosine A2A receptors (A2AR), which have an immunosuppressive effect on lymphocytes through cAMP production, the presence of spare A2AR remains to be established. We examined the situation using patients over-expressing lymphocyte A2AR and an agonist-like mAb to A2AR. We found that maximal mAb binding and functional response varied among the patients whereas the dissociation constant and half-maximal effective concentration had similar mean values (0.19 and 0.18 μM, respectively). Lymphocyte A2AR expression was correlated to plasma adenosine level and A2AR occupation but not to A2AR response. These results are consistent with a lack of a reserve of functional A2AR on human lymphocytes as a general rule and suggest that the amount and functional state of the expressed A2AR determine the maximal level of the lymphocyte response to adenosine.
Keywords: A2AR, adenosine A2A receptors; APC, adenosine plasma concentration; AU, arbitrary units; Adenosine A2A receptor; Agonist; Bmax, maximal occupation of the receptors; EC50, half-maximal effective concentration; Emax, maximal ligand response; KD, dissociation constant; Lymphocyte; NMS, neurally-mediated syncope; PBMC, peripheral blood mononuclear cells; Spare receptor; mAb.