A 2B adenosine receptor signaling and regulation.

The A 2B adenosine receptor (A 2B R) is one of the four adenosine-activated G protein-coupled receptors. In addition to adenosine, protein kinase C (PKC) was recently found to activate the A 2B R. The A 2B R is coupled to both G s and G i , as well as G q proteins in some cell types. Many primary cells and cell lines, such as bladder and breast cancer, bronchial smooth muscle, skeletal muscle, and fat cells, express the A 2B R endogenously at high levels, suggesting its potentially important role in asthma, cancer, diabetes, and other conditions. The A 2B R has been characterized as both pro- and anti-inflammatory, inducing cell type-dependent secretion of IL-6, IL-8, and IL-10. Theophylline and enprofylline have long been used for asthma treatment, although it is still not entirely clear if their A 2B R antagonism contributes to their therapeutic effects or side effects. The A 2B R is required in ischemic cardiac preconditioning by adenosine. Both A 2B R and protein kinase C (PKC) contribute to cardioprotection, and both modes of A 2B R signaling can be blocked by A 2B R antagonists. Inhibitors of PKC and A 2B R are in clinical cancer trials. Sulforaphane and other isothiocyanates from cruciferous vegetables such as broccoli and cauliflower have been reported to inhibit A 2B R signaling via reaction with an intracellular A 2B R cysteine residue (C210). A full, A 2B R-selective agonist, critical to elucidate many controversial roles of the A 2B R, is still not available, although agonist-bound A 2B R structures have recently been reported.