Figure 4. Extracellular Adenosine Uptake at “Baseline” or during “Distress.”.

Adenosine (A) can freely cross the cell membrane via equilibrative nucleoside transporters (ENTs). ENTs represent diffusion limited channels that allow free passage of adenosine through the cell membrane. During baseline conditions, only a small concentration gradient for adenosine across the cell membrane is present. Therefore, flux through ENTs is minimal. In contrast, extracellular adenosine concentrations are elevated during conditions of hypoxia, ischemia, or inflammation (“distress”). Under these conditions, adenosine flux through ENTs is directed mainly from the extracellular space towards the intracellular compartment. As long as flux through ENTs is directed from the outside towards the inside of the cell, inhibitors of ENTs (such as dipyridamole) or transcriptional mechanisms that repress ENTs will attenuate adenosine transport, and result in increased extracellular adenosine concentrations and signaling effects.