Abstract
A rapid sampling kinetic technique has been used to evaluate the nucleoside transport functions of Leishmania donovani. The results indicate that Leishmania donovani promastigotes possess two independent purine nucleoside transporters of broad but non overlapping substrate specificity. The first transports inosine, guanosine and their analogs, while the second recognizes adenosine, analogs of adenosine, and the pyrimidine nucleosides, uridine, cytidine, and thymidine. Mutant strains of Leishmania have been generated that are genetically deficient in their expression of either of the two nucleoside transport systems. The apparent Km values of the two nucleoside permeases for their purine nucleoside substrates were 0.3 - 0.6 micromolar, approximately two orders of magnitude lower than the Km values of the mammalian nucleoside transporter for these nucleosides. Wild type Leishmania were capable of concentrating purine nucleosides from the medium and converting them to the nucleotide level with great efficiency and rapidity. Inosine and adenosine transport could be distinguished by different sensitivities to sulphydryl reagents suggesting structural differences between the two carriers. Both nucleoside transporters were virtually refractory to inhibition by NBMPR and DPA, two potent inhibitors of nucleoside entry into mammalian cells. This latter observation has important chemotherapeutic implications for the treatment of diseases of parasitic origin.
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Ullman, B. 164 BIOCHEMICAL GENETIC ANALYSIS OF NUCLEOSIDE TRANSPORT IN LEISHMANIA DONOVANI PROMASTIGOTES. Pediatr Res 24, 138 (1988). https://doi.org/10.1203/00006450-198807000-00188
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DOI: https://doi.org/10.1203/00006450-198807000-00188