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Parasite-induced processes for adenosine permeation in mouse erythrocytes infected with the malarial parasite
Abstract:
In mouse erythrocytes harbouring the malarial parasite Plasmodium yoelii, three processes contributed to inward fluxes of adenosine, one of which is attributed to the native nucleoside transporter, because of the inhibitory effects of nitrobenzylthioinosine (NBMPR). New (parasite-induced) permeation processes of low NBMPR-sensitivity were (i) saturable fluxes with preference for the D enantiomer (D-Ado) and (ii) apparently unsaturable fluxes that proceeded by a channel-like route without enantiomeric selectivity. Parasite-induced fluxes of L- and D-Ado were similarly inhibited by furosemide [IC50 (concn. causing half-maximal inhibition) 15-17 microM], whereas D-Ado fluxes in uninfected erythrocytes were 10-fold less sensitive.
Insights
Malarial parasites Plasmodium yoelii induce new adenosine transport in mouse erythrocytes. These parasite-induced pathways exhibit low sensitivity to NBMPR and differ in enantiomeric selectivity and saturation kinetics.
Area of Science:
- Parasitology
- Molecular Biology
- Biochemistry
Background:
- Erythrocytes infected with Plasmodium yoelii exhibit altered nucleoside transport.
- Understanding adenosine uptake is crucial for antimalarial drug development.
Purpose of the Study:
- To characterize the mechanisms of adenosine influx in Plasmodium yoelii-infected mouse erythrocytes.
- To differentiate between native and parasite-induced nucleoside transport pathways.
Main Methods:
- Utilized nitrobenzylthioinosine (NBMPR) to identify native nucleoside transporter activity.
- Investigated parasite-induced fluxes using enantiomerically pure L- and D-adenosine (Ado).
- Assessed the effect of furosemide on adenosine transport in infected and uninfected erythrocytes.
Main Results:
- Three adenosine influx processes were identified in infected erythrocytes.
- One process involved the native nucleoside transporter, sensitive to NBMPR.
- Two novel parasite-induced pathways were characterized: saturable, D-Ado preferring, and unsaturable, channel-like.
- Furosemide inhibited parasite-induced L- and D-Ado fluxes similarly, with higher sensitivity than in uninfected cells.
Conclusions:
- Plasmodium yoelii infection significantly alters adenosine transport in mouse erythrocytes.
- The parasite induces distinct nucleoside permeation routes with unique properties.
- These findings provide insights into parasite metabolism and potential drug targets.