Abstract
Adenosine receptor activation is determined by the availability of extracellular adenosine. The tissue concentration of extracellular adenosine in turn is determined by a combination of transmembrane transport through equilibrative and concentrative nucleoside transporters and intra- and extracellular metabolism. Metabolically, adenosine levels are kept in equilibrium by adenosine-producing reactions, which include ATP-degrading enzymes and S-adenosylhomocysteine hydrolase, and adenosine-consuming enzymes, which include adenosine deaminase and adenosine kinase. The equilibrium of extracellular adenosine is critical for health, but severely compromised in a wide range of pathologies. This chapter will outline key transport- and enzyme-based mechanisms that maintain extracellular adenosine homeostasis and discuss pathological implications of disrupted adenosine homeostasis. The chapter will conclude with considerations how lifestyle choices such as sleep, exercise, and diet can influence the availability of extracellular adenosine.