The A3 adenosine receptor: An enigmatic player in cell biology

Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

“…Notably, although studies in rodent mast cells and rodent animal models have firmly established the central role played by the A3R in mediating inflammatory processes, including bronchoconstriction, hypotension, and cutaneous allergic reactions (23)(24)(25)(26), the role of the A3R in humans remained controversial. The literature split between reports revealing proinflammatory functions of the A3R, as opposed to evidence demonstrating anti-inflammatory and protective outcomes have led Gessi et al to coin the A3R as the "Dr. Jekyll and Mr. Hyde" of the inflammatory reaction (27). Indeed, unlike most GPCRs, the rodent and human A3R share only 74% homology, therefore giving rise to the possibility that these receptors may couple to different G proteins and accordingly yield differential signaling.…”

Normalization of A2A and A3 adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate

“…In adjuvantinduced arthritis in rats and in PBMCs from humans with RA, MTX treatment has been shown to enhance the antiinflammatory effects of typical A 3 agonists via up-regulation of the expression of A 3 adenosine receptor (29). These data highlight the use of A 3 receptor alterations as a good therapeutic target for the development of clinically relevant candidate drugs (13,29).…”

“…There is now increasing evidence that suggests the involvement of adenosine and adenosine receptors in the process of inflammation (10)(11)(12)(13). Adenosine, a purine nucleoside that is released in response to metabolic stress, is a potent endogenous regulator, acting via 4 cell surface receptor subtypes: A 1 , A 2A , A 2B , and A 3 , which are coupled to different G proteins (14,15).…”

“…Adenosine, a purine nucleoside that is released in response to metabolic stress, is a potent endogenous regulator, acting via 4 cell surface receptor subtypes: A 1 , A 2A , A 2B , and A 3 , which are coupled to different G proteins (14,15). A 1 and A 3 receptors are negatively coupled to adenylate cyclase and exert an inhibitory effect on cAMP production (13,16). A 2A and A 2B receptors stimulate adenylate cyclase activity by increasing cAMP accumulation, which is closely associated with various antiinflammatory pathways (17)(18)(19)(20).…”

“…Many published reports describe a central role of adenosine receptors on peripheral blood mononuclear cells (PBMCs) in mechanisms of inflammation (13)(14)(15). Moreover, adenosine receptor stimulation has been shown to have a differential effect on the release of proinflammatory cytokines (21,22).…”