Anti-inflammatory and cytoprotective effects of inosine

Inosine can be formed intracellularly as well as extracellularly. The two major routes for the intracellular formation of inosine are the deamination of adenosine to inosine by intracellular adenosine deaminase and the dephosphorylation of inosine monophosphate to inosine by 5′-nucleotidase (Figure 15.1). This deamination of adenosine to inosine occurs mainly at high intracellular adenosine concentrations associated with hypoxia, ischemia, and other forms of cellular stress. 1 Once inosine reaches high concentrations inside the cell, it is shunted into the extracellular space via the operation of bidirectional equilibrative nucleoside transporters (Figure 15.1). 2 Consistent with the fact that inosine exerts its most powerful regulatory actions in the immune system (see the following text), adenosine deaminase expression is highest in lymphoid tissues. 3 The extracellular formation of inosine is the result of conversion of adenosine to inosine by extracellular (plasma or cell surface) adenosine deaminase. Similar to inosine, adenosine is liberated from cells during metabolic stress.