PMID- 17568938 OWN - NLM STAT- MEDLINE DCOM- 20071024 LR - 20210915 IS - 0074-0276 (Print) IS - 0074-0276 (Linking) VI - 102 IP - 3 DP - 2007 Jun TI - Antimalarial drugs disrupt ion homeostasis in malarial parasites. PG - 329-34 AB - Plasmodium chabaudi malaria parasite organelles are major elements for ion homeostasis and cellular signaling and also target for antimalarial drugs. By using confocal imaging of intraerythrocytic parasites we demonstrated that the dye acridine orange (AO) is accumulated into P. chabaudi subcellular compartments. The AO could be released from the parasite organelles by collapsing the pH gradient with the K+/H+ ionophore nigericin (20 microM), or by inhibiting the H+-pump with bafilomycin (4 microM). Similarly, in isolated parasites loaded with calcium indicator Fluo 3-AM, bafilomycin caused calcium mobilization of the acidic calcium pool that could also be release with nigericin. Interestingly after complete release of the acidic compartments, addition of thapsigargin at 10 microM was still effective in releasing parasite intracellular calcium stores in parasites at trophozoite stage. The addition of antimalarial drugs chloroquine and artemisinin resulted in AO release from acidic compartments and also affected maintenance of calcium in ER store by using different drug concentrations. FAU - Gazarini, Marcos L AU - Gazarini ML AD - Departamento de Fisiologia, Instituto de Biociencias, Universidade de Sao Paulo, Suo Paulo, Brasil. cgarcia@usp.br FAU - Sigolo, Carlos A O AU - Sigolo CA FAU - Markus, Regina P AU - Markus RP FAU - Thomas, Andrew P AU - Thomas AP FAU - Garcia, Celia R S AU - Garcia CR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Brazil TA - Mem Inst Oswaldo Cruz JT - Memorias do Instituto Oswaldo Cruz JID - 7502619 RN - 0 (Antimalarials) RN - 0 (Artemisinins) RN - 0 (Fluorescent Dyes) RN - 0 (Ion Channels) RN - 886U3H6UFF (Chloroquine) RN - 9RMU91N5K2 (artemisinin) RN - F30N4O6XVV (Acridine Orange) SB - IM MH - Acridine Orange MH - Animals MH - Antimalarials/*pharmacology MH - Artemisinins/pharmacology MH - Chloroquine/pharmacology MH - Erythrocytes/*parasitology MH - Female MH - Fluorescent Dyes MH - Homeostasis/*drug effects MH - Hydrogen-Ion Concentration MH - Ion Channels/*drug effects/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Microscopy, Confocal MH - Plasmodium chabaudi/*drug effects EDAT- 2007/06/15 09:00 MHDA- 2007/10/25 09:00 CRDT- 2007/06/15 09:00 PHST- 2007/02/08 00:00 [received] PHST- 2007/06/15 09:00 [pubmed] PHST- 2007/10/25 09:00 [medline] PHST- 2007/06/15 09:00 [entrez] AID - S0074-02762007000300012 [pii] AID - 10.1590/s0074-02762007000300012 [doi] PST - ppublish SO - Mem Inst Oswaldo Cruz. 2007 Jun;102(3):329-34. doi: 10.1590/s0074-02762007000300012.