AI Article Synopsis
- The malaria parasite Plasmodium falciparum activates new permeation pathways (NPP) in infected human red blood cells, allowing the movement of various substances.
- Tests with known VRAC inhibitors showed that mefloquine, tamoxifen, and clomiphene did not significantly affect this transport at high concentrations.
- Mefloquine inhibits parasite growth at low concentrations, suggesting its antimalarial effect is not linked to blocking the NPP, indicating no evidence that NPP and VRAC are the same.
Article Abstract
The malaria parasite Plasmodium falciparum activates new permeation pathways (NPP) in the host cell membrane of infected human red blood cells (RBCs), which are permeable to anions, cations and a range of organic solutes. It has been suggested from inhibitor and substrate selectivity studies that the NPP may be identical to the volume-activated anion channel (VRAC) present in many mammalian cell types. Here we have tested several known inhibitors of VRAC on the transport of choline and lactate in malaria-infected human RBCs and on parasite growth. Mefloquine, tamoxifen and clomiphene were all without effect on malaria-induced transport at concentrations up to 10 microM and only mefloquine (IC(50) = 24 nM) and, to a lesser degree, clomiphene (IC(50) = 6.2 microM) inhibited parasite growth below this level. It is concluded that the antimalarial effect of mefloquine does not involve the inhibition of malaria-induced transport via the NPP and there is no evidence at present for VRAC and the NPP being identical.
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| http://dx.doi.org/10.1016/j.bcmd.2004.01.004 | DOI Listing |
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