| Identification of a chloroquine importer in Plasmodium falciparum - Difference in import kinetics are genetically linked with the chloroquine-resistant phenotype |
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| Author(s): Sanchez CP, Wunsch S, Lanzer M |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 272 Issue: 5 Pages: 2652-2658 Published: JAN 31 1997 |
| Times Cited: 66 References: 36 |
| Abstract: We demonstrate that uptake of the antimalarial drug chloroquine is temperature dependent, saturable, and inhibitable in Plasmodiun falciparum. These features are indicative of carrier mediated transport and suggest that a P. falciparum-encoded protein facilitates chloroquine import. Although both chloroquine-resistant and susceptible parasite isolates exhibit facilitated chloroquine uptake, the kinetics differ. Chloroquine-resistant parasite isolates consistently have an import mechanism with a lower transport activity and a reduced affinity for chloroquine. These differences in uptake kinetics are linked with chloroquine resistance in a genetic cross. These data suggest that changes in chloroquine import kinetics constitute a minimal and necessary event in the generation of the resistant phenotype. Competitive inhibition of chloroquine uptake by amiloride derivatives further suggests that chloroquine import is mediated by a plasmodial Na+/H+ exchanger. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV WURZBURG, ZENTRUM INFEKT FORSCH, D-97070 WURZBURG, GERMANY |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: WE667 |
| ISSN: 0021-9258 |