A_2b adenosine receptors can change their spots

Abstract

Recently, a central role for the A2b adenosine receptor in a variety of cardiovascular functions including inflammation, erectile function, coronary artery dilation, asthma and cardioprotection has been demonstrated. Despite this evidence, the low-affinity A2b adenosine receptor is still poorly understood. This receptor appears to be very promiscuous in its coupling. In most tissues, it couples to Gs much like its cousin, the A2a adenosine receptor, but in mast cells and now, most recently, in cardiac fibroblasts, the A2b receptor also couples to Gq. Because of its low affinity, this receptor was originally thought unlikely to play any important physiological role. But the sensitivity of A2b adenosine receptors can be greatly increased by interaction with protein kinase C (PKC) making this receptor, under various conditions, both an activator and a target of PKC. We have recently documented a third coupling involving Gi. This plasticity and versatility of A2b adenosine receptors position them as potential triggers of signalling in multiple signalling cascades in many physiological responses, making this a most interesting receptor indeed.

Adenosine A2b receptors control A1 receptor‐mediated inhibition of synaptic transmission in the mouse hippocampus

“…One possibility would be a direct heteromerisation between A 2B R and A 1 R, given that A 2B R can heteromerise with different membrane proteins such as receptors (Corset et al ., ; Moriyama & Sitkovsky, ) and enzymes (Antonioli et al ., ) and A 1 R can also form dimers with different G‐protein‐coupled receptors (Gines et al ., ; Ciruela et al ., ; Kamikubo et al ., ). An alternative would be an ability of A 2B R to trigger an intracellular cross talk through its diverse G‐protein coupling (Ryzhov et al ., ; Cohen et al ., ; Liu et al ., ) to functionally desensitise A 1 R (Ciruela et al ., ; Nie et al ., ; Hashimi et al ., ; Lopes et al ., ), in a manner analogous to the ability of A 2B R to control ion channels (Garção et al ., ), G protein coupled receptors (Feoktistov & Biaggioni, ; Conde et al ., ) or growth factor receptors (Corset et al ., ). Further studies will be required to clarify the mechanism underlying the ability of A 2B R to functionally desensitise A 1 R in nerve terminals.…”

“…The other adenosine receptors, namely adenosine A 2B receptors (A 2B R), have low expression levels in the brain (Dixon et al ., ). A 2B R are recognised as G s/q ‐protein‐coupled receptors (Feoktistov & Biaggioni, ), although they can interact with different G‐protein‐coupled receptors to recruit other G‐proteins (Ryzhov et al ., ; Cohen et al ., ; Liu et al ., ). Our knowledge about A 2B R mostly stems from their peripheral roles controlling cardiac myocite contractility, intestinal tone, asthma, inflammation, cancer and diabetes (Feoktistov & Biaggioni, ; Headrick et al ., ).…”

Adenosine Attenuates Human Coronary Artery Smooth Muscle Cell Proliferation by Inhibiting Multiple Signaling Pathways That Converge on Cyclin D

“…In mast cells 57 and cardiac fibroblasts 58 A 2B receptors couple to protein kinase C, and it is conceivable that this also occurs in HCASMCs. However, if so this would probably not contribute to inhibition of HCASMC proliferation because our previous studies suggest that PKC is involved in stimulating, rather than inhibiting, VSMC proliferation 59 .…”

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

“…Others have reported that A 2b promotes T reg -cell differentiation and limits inflammatory injury 120 . A 2b signals by multiple pathways; not only does A 2b increase cAMP via coupling to G s proteins but they might also signal via G q and G i proteins, thereby explaining their cAMP-independent effects on generation of IL-6 121 .…”