Endothelial cell uptake of adenosine in canine skeletal muscle

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Abstract
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.