Endothelial cell uptake of adenosine in canine skeletal muscle

The vascularly isolated muscles in the hindlimbs of five dogs were perfused with an oxygenated physiological salt solution. The extractions of adenosine and of a nontransported analogue of adenosine, 9-beta-D-arabinofuranosyl hypoxanthine (AraH), were determined by the single-pass indicator-dilution technique. A bolus containing [125I]albumin (reference tracer), [14C]adenosine, and [3H]AraH was injected into the artery while samples of venous effluent were collected over the next minute. This injection was repeated with dipyridamole (10(-5) M) in the perfusate. Early extractions of AraH (EAra) and adenosine (EAdo) under control conditions were 48 +/- 4 and 80 +/- 4%, respectively. In the presence of dipyridamole, EAra was unchanged (47 +/- 5) while EAdo decreased to 45 +/- 7%. Since early extraction reflects primarily the barrier posed by endothelial cells, these results demonstrate significant endothelial uptake of adenosine. Analysis of these data using a mathematical model of blood-tissue exchange indicates that, under the conditions of these experiments, at least 78% of the adenosine taken up by skeletal muscle entered endothelial cells.