Metabolism and uptake of adenosine in rat isolated lung and its inhibition

The metabolism of adenosine perfused through the pulmonary circulation of isolated lungs from rats was investigated radiochemically. Following a 10 s infusion of radioactive [14C]- or [3H]-adenosine, the recovery of radioactivity in effluent from the lung after 1 min increased from 30% at 0.5 microM to 80% at 1 mM adenosine. Unchanged adenosine comprised the major radioactive species in effluent, being about a third of the total up to 100 microM. Uptake of radioactivity was saturable at high concentrations with an apparent Km of 215 microM. Radioactivity retained in lung comprised over 80% as ATP and about 2% as adenosine at all concentrations. Perfusion of lungs with Krebs solution containing dipyridamole (1-100 microM) or adenine (10 microM) increased the rate of radioactive efflux, decreased uptake of radioactivity by lung and decreased metabolites of adenosine (inosine and hypoxanthine) in the effluent. Dipyridamole (10 microM) was more potent in decreasing uptake in guinea-pig lungs than in rat lungs. From these results we conclude that the pulmonary circulation in rat lung exhibits a significant inactivation process for adenosine. The isolated lung provides a convenient preparation for studying in situ pharmacological or pathological modifications of this vascular inactivation process.