Figure 1.

Main mechanisms involved in the control of extracellular levels of adenosine in neuronal cells. Adenosine (ADO) can be formed extracellularly from the breakdown of released ATP through a cascade of ectoenzymes, the last step being hydrolysis of AMP by ecto-5′-nucleotidase. Adenosine is also released as such through equilibrative transporters; as the intracellular adenosine concentrations are kept low, mainly due to the activity of adenosine kinase (3), and as considerable amounts of adenosine are formed from released ATP, the main direction of adenosine transport is inwards. However, under some conditions (e.g. low oxygen, low glucose, depolarization), the intracellular adenosine levels rise and outward transport of adenosine occurs. Interconversion of adenosine into S-adenosyl-homocysteine (SAH) or deamination into inosine (INO) also contributes to the low intracellular adenosine levels. AMP, adenosine 5′-monophosphate; ATP, adenosine 5′-triphosphate.