ATP release from erythrocytes: A role of adenosine

BACKGROUND: The oxygen required to meet metabolic needs of all tissues is delivered by the red blood cell (RBC), a small, flexible cell which, in mammals, is devoid of a nucleus and mitochondria. Despite its simple appearance, this cell has an important role in its own distribution, enabling the delivery of oxygen to precisely meet localized metabolic need. When red blood cells enter in hypoxic area, a signalling pathway is activated within the cell, resulting in the release of ATP in amounts adequate to activate purinergic receptors on vascular endothelium, which trigger secretion of nitric oxide and other factors resulting in vasodilatation. OBJECTIVE: The present study investigates the effect of adenosine exposure on this molecular mechanism. METHODS AND RESULTS: We report that RBC in the presence of adenosine in low oxygen conditions, ATP release increase after 24 h exposure. Adenosine induced-ATP release in deoxygenated red blood cell show data similar to that of RBC in high oxygen conditions: (1) RBC after band 3 modification by 4,4'- diisothio-cyanatostilbene- 2,2'-disulphonic acid; (2) CO-treated RBC. In the presence of Sphingosine kinase (SphK1) inhibitor, adenosine mediated effects on ATP release were abolished. Activity of adenylate cyclase increase following to adenosine exposure, on the contrary red cell phosphofructokinase is not modified within the RBC in the presence of adenosine. CONCLUSION: Our data support involvement of band 3/deoxyHb binding and adenylate cyclase in the pathway responsible for ATP release from RBC following exposure to adenosine.