Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
AAAS Promotion

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 27 November 1987:
Vol. 238. no. 4831, pp. 1283 - 1285
DOI: 10.1126/science.3317830
Prev | Table of Contents | Next

Articles

Science, Vol 238, Issue 4831, 1283-1285
Copyright © 1987 by American Association for the Advancement of Science

articles

Efflux of chloroquine from Plasmodium falciparum: mechanism of chloroquine resistance

DJ Krogstad, IY Gluzman, DE Kyle, AM Oduola, SK Martin, WK Milhous, and PH Schlesinger

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.

Chloroquine-resistant Plasmodium falciparum accumulate significantly less chloroquine than susceptible parasites, and this is thought to be the basis of their resistance. However, the reason for the lower accumulation of chloroquine was unknown. The resistant parasite has now been found to release chloroquine 40 to 50 times more rapidly than the susceptible parasite, although their initial rates of chloroquine accumulation are the same. Verapamil and two other calcium channel blockers, as well as vinblastine and daunomycin, each slowed the release and increased the accumulation of chloroquine by resistant (but not susceptible) Plasmodium falciparum. These results suggest that a higher rate of chloroquine release explains the lower chloroquine accumulation, and thus the resistance observed in resistant Plasmodium falciparum.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A verapamil-sensitive chloroquine-associated H+ leak from the digestive vacuole in chloroquine-resistant malaria parasites.
A. M. Lehane, R. Hayward, K. J. Saliba, and K. Kirk (2008)
J. Cell Sci. 121, 1624-1632
   Abstract »    Full Text »    PDF »
Drug-Regulated Expression of Plasmodium falciparum P-Glycoprotein Homologue 1: a Putative Role for Nuclear Receptors.
D. J. Johnson, A. Owen, N. Plant, P. G. Bray, and S. A. Ward (2008)
Antimicrob. Agents Chemother. 52, 1438-1445
   Abstract »    Full Text »    PDF »
Molecular Epidemiology of Malaria in Cameroon. XXVI. Twelve-Year In Vitro and Molecular Surveillance of Pyrimethamine Resistance and Experimental Studies to Modulate Pyrimethamine Resistance.
R. Tahar and L. K. Basco (2007)
Am J Trop Med Hyg 77, 221-227
   Abstract »    Full Text »    PDF »
Specific Inhibition of the Plasmodial Surface Anion Channel by Dantrolene.
G. Lisk, M. Kang, J. V. Cohn, and S. A. Desai (2006)
Eukaryot. Cell 5, 1882-1893
   Abstract »    Full Text »    PDF »
DETECTION OF BENZIMIDAZOLE RESISTANCE-ASSOCIATED MUTATIONS IN THE FILARIAL NEMATODE WUCHERERIA BANCROFTI AND EVIDENCE FOR SELECTION BY ALBENDAZOLE AND IVERMECTIN COMBINATION TREATMENT.
A. E. SCHWAB, D. A. BOAKYE, D. KYELEM, and R. K. PRICHARD (2005)
Am J Trop Med Hyg 73, 234-238
   Abstract »    Full Text »    PDF »
Dictyostelium discoideum Expresses a Malaria Chloroquine Resistance Mechanism upon Transfection with Mutant, but Not Wild-type, Plasmodium falciparum Transporter PfCRT.
B. Naude, J. A. Brzostowski, A. R. Kimmel, and T. E. Wellems (2005)
J. Biol. Chem. 280, 25596-25603
   Abstract »    Full Text »    PDF »
The Malaria Parasite's Chloroquine Resistance Transporter is a Member of the Drug/Metabolite Transporter Superfamily.
R. E. Martin and K. Kirk (2004)
Mol. Biol. Evol. 21, 1938-1949
   Abstract »    Full Text »    PDF »
Evidence for Activation of Endogenous Transporters in Xenopus laevis Oocytes Expressing the Plasmodium falciparum Chloroquine Resistance Transporter, PfCRT.
S. Nessler, O. Friedrich, N. Bakouh, R. H. A. Fink, C. P. Sanchez, G. Planelles, and M. Lanzer (2004)
J. Biol. Chem. 279, 39438-39446
   Abstract »    Full Text »    PDF »
History, Dynamics, and Public Health Importance of Malaria Parasite Resistance.
A. O. Talisuna, P. Bloland, and U. D'Alessandro (2004)
Clin. Microbiol. Rev. 17, 235-254
   Abstract »    Full Text »    PDF »
Chloroquine Resistance Modulated in Vitro by Expression Levels of the Plasmodium falciparum Chloroquine Resistance Transporter.
K. L. Waller, R. A. Muhle, L. M. Ursos, P. Horrocks, D. Verdier-Pinard, A. B. S. Sidhu, H. Fujioka, P. D. Roepe, and D. A. Fidock (2003)
J. Biol. Chem. 278, 33593-33601
   Abstract »    Full Text »    PDF »
NEW HAPLOTYPES OF THE PLASMODIUM FALCIPARUM CHLOROQUINE RESISTANCE TRANSPORTER (PFCRT) GENE AMONG CHLOROQUINE-RESISTANT PARASITE ISOLATES.
H. S. NAGESHA, G. J. CASEY, K. H. RIECKMANN, D. J. FRYAUFF, B. S. LAKSANA, J. C. REEDER, J. D. MAGUIRE, and J. K. BAIRD (2003)
Am J Trop Med Hyg 68, 398-402
   Abstract »    Full Text »    PDF »
In vitro susceptibility to a new antimalarial organometallic analogue, ferroquine, of Plasmodium falciparum isolates from the Haut-Ogooue region of Gabon.
C. Atteke, J. M. M. Ndong, A. Aubouy, L. Maciejewski, J. Brocard, J. Lebibi, and P. Deloron (2003)
J. Antimicrob. Chemother. 51, 1021-1024
   Abstract »    Full Text »    PDF »
ANALYSIS OF PFCRT, PFMDR1, DHFR, AND DHPS MUTATIONS AND DRUG SENSITIVITIES IN PLASMODIUM FALCIPARUM ISOLATES FROM PATIENTS IN VIETNAM BEFORE AND AFTER TREATMENT WITH ARTEMISININ.
T. NGO, M. DURAISINGH, M. REED, D. HIPGRAVE, B. BIGGS, and A. F. COWMAN (2003)
Am J Trop Med Hyg 68, 350-356
   Abstract »    Full Text »    PDF »
Simple In Vitro Assay for Determining the Sensitivity of Plasmodium vivax Isolates from Fresh Human Blood to Antimalarials in Areas where P. vivax Is Endemic.
B. M. Russell, R. Udomsangpetch, K. H. Rieckmann, B. M. Kotecka, R. E. Coleman, and J. Sattabongkot (2003)
Antimicrob. Agents Chemother. 47, 170-173
   Abstract »    Full Text »    PDF »
Chloroquine Resistance in Plasmodium falciparum Malaria Parasites Conferred by pfcrt Mutations.
A. B. S. Sidhu, D. Verdier-Pinard, and D. A. Fidock (2002)
Science 298, 210-213
   Abstract »    Full Text »    PDF »
In Vitro Increase in Chloroquine Accumulation Induced by Dihydroethano- and Ethenoanthracene Derivatives in Plasmodium falciparum-Parasitized Erythrocytes.
B. Pradines, S. Alibert, C. Houdoin, C. Santelli-Rouvier, J. Mosnier, T. Fusai, C. Rogier, J. Barbe, and D. Parzy (2002)
Antimicrob. Agents Chemother. 46, 2061-2068
   Abstract »    Full Text »    PDF »
Relationship between Chloroquine Toxicity and Iron Acquisition in Saccharomyces cerevisiae.
L. R. Emerson, M. E. Nau, R. K. Martin, D. E. Kyle, M. Vahey, and D. F. Wirth (2002)
Antimicrob. Agents Chemother. 46, 787-796
   Abstract »    Full Text »    PDF »
Alternative Mutations at Position 76 of the Vacuolar Transmembrane Protein PfCRT Are Associated with Chloroquine Resistance and Unique Stereospecific Quinine and Quinidine Responses in Plasmodium falciparum.
R. A. Cooper, M. T. Ferdig, X.-Z. Su, L. M. B. Ursos, J. Mu, T. Nomura, H. Fujioka, D. A. Fidock, P. D. Roepe, and T. E. Wellems (2002)
Mol. Pharmacol. 61, 35-42
   Abstract »    Full Text »    PDF »
Ferrocene-chloroquine analogues as antimalarial agents: in vitro activity of ferrochloroquine against 103 Gabonese isolates of Plasmodium falciparum.
B. Pradines, T. Fusai, W. Daries, V. Laloge, C. Rogier, P. Millet, E. Panconi, M. Kombila, and D. Parzy (2001)
J. Antimicrob. Chemother. 48, 179-184
   Abstract »    Full Text »    PDF »
Membrane Transport in the Malaria-Infected Erythrocyte.
K. Kirk (2001)
Physiol Rev 81, 495-537
   Abstract »    Full Text »    PDF »
ABC transporters required for endocytosis and endosomal pH regulation in Dictyostelium.
D. T. Brazill, L. R. Meyer, R. D. Hatton, D. A. Brock, and R. H. Gomer (2001)
J. Cell Sci. 114, 3923-3932
   Abstract »    Full Text »    PDF »
Citalopram Enhances the Activity of Chloroquine in Resistant Plasmodium in Vitro and in Vivo.
S. G. Evans, N. Butkow, C. Stilwell, M. Berk, N. Kirchmann, and I. Havlik (1998)
J. Pharmacol. Exp. Ther. 286, 172-174
   Abstract »    Full Text »
In Vitro Antimalarial Activity of a New Organometallic Analog, Ferrocene-Chloroquine.
O. Domarle, G. Blampain, H. Agnaniet, T. Nzadiyabi, J. Lebibi, J. Brocard, L. Maciejewski, C. Biot, A. J. Georges, and P. Millet (1998)
Antimicrob. Agents Chemother. 42, 540-544
   Abstract »    Full Text »
Differential Stimulation of the Na+/H+ Exchanger Determines Chloroquine Uptake in Plasmodium falciparum.
S. Wunsch, C. P. Sanchez, M. Gekle, L. Grosse-Wortmann, J. Wiesner, and M. Lanzer (1998)
J. Cell Biol. 140, 335-345
   Abstract »    Full Text »    PDF »
Assessment of three in vitro tests and an in vivo test for chloroquine resistance in Plasmodium falciparum clinical isolates [In Process Citation].
J Bickii, L. Basco, and P Ringwald (1998)
J. Clin. Microbiol. 36, 243-247
   Abstract »    Full Text »
Detection of RAPD Markers Correlated with Chloroquine Resistance in Plasmodium falciparum.
P. Lescuyer, S. Picot, V. Bracchi, J. Burnod, J. Austin, A. Perard, and P. Ambroise-Thomas (1997)
Genome Res. 7, 747-753
   Abstract »    Full Text »    PDF »
Probing the Chloroquine Resistance Locus of Plasmodium falciparum with a Novel Class of Multidentate Metal(III) Coordination Complexes.
D. E. Goldberg, V. Sharma, A. Oksman, I. Y. Gluzman, T. E. Wellems, and D. Piwnica-Worms (1997)
J. Biol. Chem. 272, 6567-6572
   Abstract »    Full Text »    PDF »
Identification of a Chloroquine Importer in Plasmodium falciparum. DIFFERENCES IN IMPORT KINETICS ARE GENETICALLY LINKED WITH THE CHLOROQUINE-RESISTANT PHENOTYPE.
C. P. Sanchez, S. Wunsch, and M. Lanzer (1997)
J. Biol. Chem. 272, 2652-2658
   Abstract »    Full Text »    PDF »
Verapamil Reversal of Chloroquine Resistance in the Malaria Parasite Plasmodium falciparum Is Specific for Resistant Parasites and Independent of the Weak Base Effect.
J. A. Martiney, A. Cerami, and A. F. G. Slater (1995)
J. Biol. Chem. 270, 22393-22398
   Abstract »    Full Text »    PDF »
The challenge of malaria.
L. Miller (1992)
Science 257, 36-37
   PDF »
Amplification of a gene related to mammalian mdr genes in drug-resistant Plasmodium falciparum.
C. Wilson, A. Serrano, A Wasley, M. Bogenschutz, A. Shankar, and D. Wirth (1989)
Science 244, 1184-1186
   Abstract »    PDF »
Reversal of chloroquine resistance in malaria parasite Plasmodium falciparum by desipramine.
A. Bitonti, A Sjoerdsma, P. McCann, D. Kyle, A. Oduola, R. Rossan, W. Milhous, and D. Davidson Jr (1988)
Science 242, 1301-1303
   Abstract »    PDF »
HOW DOES CHLOROQUINE RESISTANCE OCCUR IN MALARIA?.
(1987)
Journal Watch (General) 1987, 6
   Full Text »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)