Species differences in sensitivity of nucleoside transport in erythrocytes and cultured cells to inhibition by nitrobenzylthioinosine, dipyridamole, dilazep and lidoflazine

Abstract

Differences in sensitivity of uridine transport in erythrocytes and cultured cells to inhibition by dipyridamole, dilazep and lidoflazine were largely species-specific; uridine transport in human cells, and probably in pig and rabbit cells, was 2–3- and 10-times more sensitive to inhibition by dipyridamole (IC 50 approx. 50 nM) and about 10- and 20-times more sensitive to dilazep inhibition (IC 50 approx. 5 nM) than transport in mouse and rat cells, respectively. Uridine transport in human erythrocytes and HeLa cells was strongly inhibited by lidoflazine (IC 50 10–140 nM), whereas that in both mouse and rat cells was highly resistant ( IC 50 > 10 μ M ). Superimposed on species-specific differences were some cell type specific differences in sensitivity of nucleoside transport to these inhibitors. Uridine transport in Walker 256 rat carcinoma cells was more resistant to dipyridamole and dilazep than that of other rat cells. Transport in human Hep-2 cells was more resistant to lidoflazine (IC 50 2000 nM) than that of human erythrocytes and HeLa cells, whereas it showed similar sensitivity to dilazep and dipyridamole. Uridine transport in Chinese hamster cells was also more resistant to dilazep than that of baby hamster kidney cells. In addition HeLa cells and clones thereof expressed uridine transporters (about 50% each) with difference of about 1000-fold in sensitivity to inhibition by dilazep (IC 50 approx. 5 nM and 5 μM, respectively)