Storage,release, uptake,and inactivation of purines

Adenine nucleotides are released into the interstitial space during platelet thrombus formation and neurotransmission. ATP has also been reported to be released from the heart and endothelial cells in some studies. Ecto ATPase, ADPase, and 5′-nucleotidase activities capable of hydrolyzing ATP sequentially to adenosine are present in many cell types and may serve to terminate the actions of the nucleotides. The opposing effects of adenosine and ATP on the same cell types have suggested a modulatory role for adenosine of the actions of extracellular ATP and that the rates of hydrolysis of nucleotides might be regulated. Consistent with this it has been found that the balance between feedforward inhibition of 5′-nucleotidase by ADP and/or ATP and preferential delivery of AMP from ADPase to 5′-nucleotidase determines the rate of adenosine production and that this differs in different cell types. Alternatively, adenosine may be produced intracellularly as a result of an imbalance between energy demand and supply. There are at least two different cytosolic forms of 5′-nucleotidase. Degradation of ATP during increased metabolic activity results in an increase in intracellular AMP concentration. Either cytosolic enzyme has a high KM (2–5 mM) and would thus respond to this increase with a proportional rise in the rate of adenosine production. The nucleoside transporter is essential to allow the diffusion of adenosine to extracellular receptor sites. In general, adenosine must be taken up via the nucleoside transporter before it is inactivated either by phosphorylation by adenosine kinase in the micromolar range or by deamination by adenosine deaminase at higher concentrations. © 1993 Wiley-Liss, Inc.