| Scientific Background: | Adenosine is an endogenous nucleoside generated locally in tissues under conditions of hypoxia, ischemia, or inflammation. It modulates a variety of physiological functions in many tissues including brain and heart. It exerts its action via four specific adenosine receptors (also named P1 purinergic receptors): A1 Adenosine Receptor (A1AR), A2A Adenosine Receptor (A2AAR), A2B Adenosine Receptor (A2BAR), and A3 Adenosine Receptor (A3AR). All are integral membrane proteins and members of the G Protein-Coupled Receptor superfamily. The various adenosine receptors can be distinguished on the basis of their differential selectivity for adenosine analogs. The A2 Adenosine receptor subtype was subdivided according to affinity for adenosine; A2AAR has high affinity and A2BAR has low affinity for adenosine. A2BAR is expressed in mast cells, neutrophils, monocytes, macrophages, dendritic cells, T cells, bronchial epithelium, intestinal epithelium, smooth muscle, brain, and other cells. In intestinal epithelia, A2BAR was found to be the major adenosine receptor subtype expressed and is thought to be involved in diarrheal diseases. It is also believed to be involved in the pathogenesis of chronic airway inflammatory diseases. Antagonists of A2BAR may be effective for the treatment of inflammatory gastrointestinal tract disorders4 as well as asthma and chronic obstructive pulmonary disease. |
