TY - JOUR
T1 - The effect of mefloquine and volume-regulated anion channel inhibitors on induced transport in Plasmodium falciparum-infected human red blood cells
AU - Staines, Henry M.
AU - Dee, Belinda C.
AU - Shen, Meng Ru
AU - Ellory, J. Clive
PY - 2004/5
Y1 - 2004/5
N2 - 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 μM and only mefloquine (IC50 = 24 nM) and, to a lesser degree, clomiphene (IC50 = 6.2 μM) 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.
AB - 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 μM and only mefloquine (IC50 = 24 nM) and, to a lesser degree, clomiphene (IC50 = 6.2 μM) 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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U2 - 10.1016/j.bcmd.2004.01.004
DO - 10.1016/j.bcmd.2004.01.004
M3 - Article
C2 - 15121089
AN - SCOPUS:2342535202
VL - 32
SP - 344
EP - 348
JO - Blood Cells, Molecules, and Diseases
JF - Blood Cells, Molecules, and Diseases
SN - 1079-9796
IS - 3
ER -