Adenosine, oxidative stress and cytoprotection

Adenosine, a metabolite of ATP, serves a number of important physiological roles in the body. These actions contribute to sedation, bradycardia, vasorelaxation, inhibition of lipolysis and regulation of the immune system and are mediated, in part, through activation of three distinct adenosine receptor (AR) subtypes. To date, four receptor types have been cloned: A(1), A(2A), A(2B) and A(3). It is becoming increasing clear that adenosine contributes significantly to cytoprotection, a function mediated principally by the A(1)AR and A(3)AR, In this review, we survey the literature on the role of adenosine and the mechanisms underlying cytoprotection and ischemic preconditioning, a process characterized by cytoprotection derived from repeated brief ischemic challenges. An important recent observation is that the expression of several AR subtypes could be regulated by oxidative stress to provide a greater cytoprotective role. Thus, like other proteins known to be regulated during ischemia, the A(1)AR and A(3)AR can be considered as being inducible receptors.