A(2b) adenosine receptors can change their spots.

Recently, a central role for the A(2b) 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 A(2b) adenosine receptor is still poorly understood. This receptor appears to be very promiscuous in its coupling. In most tissues, it couples to G(s) much like its cousin, the A(2a) adenosine receptor, but in mast cells and now, most recently, in cardiac fibroblasts, the A(2b) receptor also couples to G(q). Because of its low affinity, this receptor was originally thought unlikely to play any important physiological role. But the sensitivity of A(2b) 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 G(i). This plasticity and versatility of A(2b) adenosine receptors position them as potential triggers of signalling in multiple signalling cascades in many physiological responses, making this a most interesting receptor indeed.