Uptake and metabolism of adenosine by pig aortic endothelial and smooth-muscle cells in culture

Abstract

Adenosine, a potent vasodilator, is transported very efficiently by pig aortic endothelium in monolayer culture (approx. 50 pmol/min per 106 cells at 2 μM). Uptake proceeds by diffusion at high (millimolar) substrate concentrations, and by two discrete transport processes (Km approx. 3 μM and 250 μM) at lower concentrations. Over 90% of the adenosine taken up at 10 μM or 100μM is rapidly converted into adenine nucleotides (mainly ATP). The high-affinity process is selectively inhibited by dipyridamole and by nitrobenzylthioinosine. Adenine preferentially inhibits the lower-affinity process, papaverine inhibits both transport processes, and inosine has no significant effect. Pig aortic smooth-muscle cells in culture show no high-affinity transport system for adenosine; uptake is much slower at low concentrations than that by endothelium (approx. 5 pmol/min per 106 cells at 2 μM). Over 80% of the incorporated adenosine at 10 μM or 100 μM is rapidly converted into adenine nucleotides. The uptake of adenosine by smooth-muscle cells is powerfully inhibited by adenine, but dipyridamole is much less potent than in endothelium. It is concluded that endothelial cells are mainly responsible for the removal of circulating adenosine.