title: Effect of dipyridamole on transport and phosphorylation of thymidine and 3'-azido-3'-deoxythymidine in human monocyte/macrophages.
abstract: 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.
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: G V
authors.initials: GV
authors.lastname: Betageri
authors.forename: J
authors.initials: J
authors.lastname: Szebeni
authors.forename: K
authors.initials: K
authors.lastname: Hung
authors.forename: S S
authors.initials: SS
authors.lastname: Patel
authors.forename: L M
authors.initials: LM
authors.lastname: Wahl
authors.forename: M
authors.initials: M
authors.lastname: Corcoran
authors.forename: J N
authors.initials: JN
authors.lastname: Weinstein
mesh_terms: 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*
chemical_list: D015215:Zidovudine; D004176:Dipyridamole; D013936:Thymidine