Inhibition of adenosine uptake in human erythrocytes by adenosine-5'-carboxamides, xylosyladenine, dipyridamole, hexobendine, and p-nitrobenzylthioguanosine

Adenosine uptake in human erythrocytes at 0° consists of a saturable and a concentration-proportional component, the latter seems to represent uptake into a pericellulai compartment inaccessible to inulin. Xylosyladenine and derivatives of adenosine-5'-carboxamide were found to be weak inhibitors of the saturable component of adenosine uptake with apparent Ki values at least one order of magnitude higher than the apparent Km for adenosine (2.4 × 10−6 M). The affinity of the adenine nucleosides to the saturable uptake process appears to depend not only on the 3'-hydroxy] group and its erythro-configuration but also on the 5'-substituent. Dipyridamole, hexobendine, and p-nitrobenzylthioguanosine, by contrast, had Ki values at least one order of magnitude lower than the Km for adenosine. The steric requirements for binding of the adenine furanosides to the putative smooth muscle receptors mediating vasodilation. on the the one hand, and to the saturable cellular uptake mechanism, on the other hand, were found to be different.