Identification of distinct accumulation sites of 4-aminoquinoline in chloroquine sensitive and resistant Plasmodium berghei strains.
We report the synthesis of an analogue of chloroquine (CQA) which can be used as a probe to visualize accumulation of 4-aminoquinoline by electron microscopy. A mouse monoclonal antibody against CQA was raised and used for immunodetection by the protein-A gold method on ultrathin cryosections, of CQA treated parasites. We demonstrate that in a P. berghei chloroquine(CQ)-sensitive strain (N strain) the chloroquine analogue used accumulates in the endocytic vacuoles where hemoglobin (Hb) degradation is occurring. In contrast, in a P. berghei CQ-resistant strain (RC strain) the probe was found scattered all over the cytoplasm of the parasite. This result suggests that endocytic vacuoles of the parasite could constitute the site of antimalarial action of CQ.
D000634:Aminoquinolines / Q000378:metabolism*; D000818:Animals; D002451:Cell Compartmentation; D002738:Chloroquine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D004351:Drug Resistance; D004705:Endocytosis; D010962:Plasmodium berghei / Q000187:drug effects* / Q000378:metabolism
D000634:Aminoquinolines; D002738:Chloroquine; C001920:4-aminoquinoline