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, vasor elaxation, inhibition of lipolysis and regulation of the immune system and are mediated, in part, through activation of three distinct adenosine recep tor (AR) subtypes. To date, four receptor types have been cloned: A(1), A(2 A), A(2B) and A(3). It is becoming increasing clear that adenosine contribu tes 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 precon ditioning, a process characterized by cytoprotection derived from repeated brief ischemic challenges. An important recent observation is that the expr ession of several AR subtypes could be regulated by oxidative stress to pro vide a greater cytoprotective role. Thus, like other proteins known to be r egulated during ischemia, the A(1)AR and A(3)AR can be considered as being inducible receptors.