A(3) adenosine receptor ligands: History and perspectives

Adenosine regulates many physiological functions through specific cell memb rane receptors. On the basis of pharmacological studies and molecular cloni ng, four different adenosine receptors have been identified and classified as A(1), A(2A), A(2B), and A(3). These adenosine receptors are members of t he G-protein-coupled receptor family. While adenosine A(1) and A(2A) recept or subtypes have been pharmacologically characterized through the use of se lective ligands, the A(3) adenosine receptor subtype is presently under stu dy in order to better understand its physio-pathological functions. Activat ion of adenosine A(3) receptors has been shown to stimulate phospholipase C and D and to inhibit adenylate cyclase. Activation of A(3) adenosine recep tors also causes the release of inflammatory mediators such as histamine fr om mast cells. These mediators are responsible for processes such as inflam mation and hypotension. It has also been suggested that the A(3) receptor p lays an important role in brain ischemia, immunosuppression, and bronchospa sm in several animal models. Based on these results, highly selective A(3) adenosine receptor agonists and/or antagonists have been indicated as poten tial drugs for the treatment of asthma and inflammation, while highly selec tive agonists have been shown to possess cardioprotective effects. The upda ted material related to this field of research has been rationalized and ar ranged in order to offer an overview of the topic, (C) 2000 John Wiley & So ns, Inc.