Parasite-induced permeation of nucleosides in Plasmodium falciparum malaria

Abstract

A mechanism which mediates the transport of the nonphysiological nucleoside, l-adenosine, was demonstrated in Plasmodium falciparum infected erythrocytes and naturally released merozoites. l-Adenosine was not a substrate for influx in freed intraerythrocytic parasites or in normal human erythrocytes nor was l-adenosine transported in a variety of cell types including other parasitic protozoa such as Crithidia luciliae, Trichomonas vaginalis, Giardia intestinalis, or the mammalian cells, Buffalo Green Monkey and HeLa cells. l-Adenosine transport in P. falciparum infected cells was nonsaturable, with a rate of 0.13 ± 0.01 pmol/ μl cell water per s per μM l-adenosine, yet the transport was inhibited by furosemide, phloridzin and piperine with IC 50 values between 1–13 μM, distinguishing the transport pathway from simple diffusion. The channel-like permeation was selective as disaccharides were not permeable to parasitised cells. In addition, an unusual metabolic property of parasitic adenosine deaminase was found in that l-adenosine was metabolised to l-inosine by both P. falciparum infected erythrocytes and merozoites, an activity which was inhibited by 50 nM deoxycoformycin. No other cell type examined displayed this enzymic activity. The results further substantiate that nucleoside transport in P. falciparum infected cells was significantly altered compared to uninfected erythrocytes and that l-adenosine transport and metabolism was a biochemical property of Plasmodium infected cells and merozoites and not found in normal erythrocytes nor any of the other cell types investigated.