Glibenclamide and meglitinide block the transport of low molecular weight solutes into malaria-infected erythrocytes.
Following infection by the malaria parasite, human erythrocytes show increased uptake of a wide variety of low molecular weight solutes via pathways with functional characteristics different from those of the transporters of normal erythrocytes. In this study glibenclamide and meglitinide were shown to inhibit the induced transport of a sugar alcohol (sorbitol), an amino acid (threonine), an inorganic anion (Cl-) and an organic cation (choline) into human erythrocytes infected in vitro with Plasmodium falciparum. The results are consistent with the hypothesis that a diverse range of substrates enter malaria-infected cells via common pathways which have features in common with Cl- channels in other cell types. glibenclamide and meglitinide were also shown to inhibit the in vitro growth of the intracellular parasite which would suggest that these pathways may be a viable chemotherapeutic target.
University Laboratory of Physiology, Oxford, UK.
K
K
Kirk
H A
HA
Horner
D J
DJ
Spillett
B C
BC
Elford
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology*; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D010963:Plasmodium falciparum / Q000254:growth & development / Q000502:physiology*; D013012:Sorbitol / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D014044:Tolbutamide / Q000494:pharmacology
D001549:Benzamides; D002712:Chlorides; D013912:Threonine; D013012:Sorbitol; C030516:meglitinide; D014044:Tolbutamide; D002794:Choline; D005905:Glyburide