Effect of dipyridamole on transport and phosphorylation of thymidine and 3'-azido-3'-deoxythymidine in human monocyte/macrophages.
Dipyridamole (DPM), a commonly used coronary vasodilator and antithrombotic drug, was shown recently to potentiate the antiviral effect of 3'-azido-3'-deoxythymidine (AZT) in HIV-1 infected human monocyte-derived macrophages (M/M) in vitro. We report in the present study that in uninfected M/M, DPM markedly inhibited cellular uptake of [3H]thymidine (dThd) and its incorporation into the nucleotide pools, particularly the dThd-triphosphate pool. In contrast, DPM did not affect cellular uptake and phosphorylation of [3H]AZT. Since dThd counteracts the phosphorylation and antiviral action of AZT, these findings support the hypothesis that the potentiation of the anti-HIV effect of AZT is due, at least in part, to differential inhibition of nucleoside salvage.
Betageri
G V
GV
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Szebeni
J
J
Hung
K
K
Patel
S S
SS
Wahl
L M
LM
Corcoran
M
M
Weinstein
J N
JN
D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004176:Dipyridamole / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D010766:Phosphorylation; D013936:Thymidine / Q000378:metabolism*; D015215:Zidovudine / Q000378:metabolism*
D015215:Zidovudine; D004176:Dipyridamole; D013936:Thymidine