Modulation of glial cell functions by adenosine receptors

Adenosine is an endogenous neuromodulator, acting on four distinctive G-protein-coupled receptors, the A1, A2A, A2B and A3 adenosine receptors. Increased neuronal activity and, hypoxia or ischemia, result in elevated levels of adenosine reflecting changes of the metabolic state. This increases activation of the adenosine receptors. It is well appreciated that adenosine has a neuroprotective role in brain injuries. Although adenosine effects have been explained mainly by actions on nerve cells, modulation of glial functions by adenosine is likely to be important as discussed in this minireview. Thus, in astrocytes adenosine receptors modulate inter alia glycogen metabolism, glutamate transporters, astrogliosis and astrocyte swelling. Microglial cells appear to be important in regulating adenosine formation from ATP and adenosine can affect many microglial signaling pathways. Adenosine receptors on oligodendrocytes regulate white matter development.