Relations between resistance to chloroquine and acidification of endocytic vesicle of Plasmodium berghei.
In order to visualize low-pH compartments of Plasmodium berghei strains we have used a basic congener of dinitrophenol, 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine (DAMP) which concentrates in acidic compartments, and can be detected by immunocytochemistry with anti-dinitrophenol antibodies. We have demonstrated that in a P. berghei chloroquine-sensitive strain (N strain), DAMP accumulates in the endocytic vacuoles where haemoglobin degradation is occurring. These compartments which have recently been shown to concentrate 4-aminoquinoline drugs (Moreau, Prensier, Maalla & Fortier, 1986) have an acidic pH. Conversely DAMP was found scattered all over the cytoplasm in a P. berghei chloroquine-resistant strain; the same phenomenon was previously observed (Moreau et al. 1986) in the localization of a 4-aminoquinoline on this same strain. Monensin-induced swelling of acidic compartments (Boss & Morre, 1984) was used as a complementary method for the determination of low-pH compartments on P. berghei strains. All the data reported here suggest that chloroquine resistance in P. berghei RC may be related to an impairment in the acidification of endocytic vesicles.
Mahmalgi
J
J
INSERM U.42, Biologie et Biochimie Parasitaire et Fongique, Villeneuve d'Ascq, France.
Veignie
E
E
Prensier
G
G
Moreau
S
S
D000818:Animals; D002738:Chloroquine / Q000494:pharmacology*; D004136:Dinitrobenzenes / Q000032:analysis; D004351:Drug Resistance; D004705:Endocytosis; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D009682:Magnetic Resonance Spectroscopy; D008854:Microscopy, Electron; D015394:Molecular Structure; D008985:Monensin / Q000494:pharmacology; D010962:Plasmodium berghei / Q000032:analysis / Q000187:drug effects* / Q000648:ultrastructure
D004136:Dinitrobenzenes; D002738:Chloroquine; D008985:Monensin; C042432:3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine