EFFECTS OF DIPYRIDAMOLE, SOLUFLAZINE AND RELATED MOLECULES ON ADENOSINE UPTAKE AND METABOLISM BY ISOLATED HUMAN RED-BLOOD-CELLS

The suggestion that adenosine may have beneficial effects on post repe rfusion survival following cardiac ischaemia has led to the search for agents which increase the concentration of this substance in the isch emic region as a possible therapeutic approach to the treatment of ang ina and myocardial infarction. In the present study, dipyridamole, sol uflazine and lidoflazine, known inhibitors of the nucleotide exchange system, have been shown using an HPLC method to prevent the decrease i n the concentration od added adeno- sine outside human red blood cells in vitro. However, the results suggest that this effect was due to in hibition of adenosine deaminase rather than inhibition of nucleotide e xchange as had previously been suggested. The selective inhibitor of a denosine deaminase erythro-9-(2 hydroxy-9-nonyl adenosine) exhibited t he same profile of activity in the human red blood cell assay. pIC(50) values for the four compounds named above were found to be 6.80 +/- 0 .09, 6.95 +/- .03, 6.10 +/- 0.14 and 7.39 +/- 0.05 vs adenosine disapp earance observed in the extracellular incubation medium respectively. Thus, as the disappearance of adenosine outside the cells was not due to its uptake but to its catabolism, this in vitro method does not app ear to be predictive for the ability of compounds to act on adenosine uptake into cardiac myocytes. Any antiischemic action of these agents is more readily explained by an inhibition of the catabolism of adenos ine and not by the inhibition of its transport across the membrane of cardiac myocytes.