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  • Title: The effect of mefloquine and volume-regulated anion channel inhibitors on induced transport in Plasmodium falciparum-infected human red blood cells.
    Author: Staines HM, Dee BC, Shen MR, Ellory JC.
    Journal: Blood Cells Mol Dis; 2004; 32(3):344-8. PubMed ID: 15121089.
    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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