Mechanism of stimulation of Ca2+ uptake by miconazole and ethidium bromide in yeasts: role of vacuoles in Ca2+ detoxification.
The antifungal antibiotic miconazole and the cationic dye ethidium bromide, both caused K+ efflux, membrane depolarization and intracellular acidification in the yeast Saccharomyces cerevisiae. Whereas miconazole inhibited the activity of the plasma membrane H+-ATPase, no such inhibition was observed using ethidium bromide at concentrations up to 600 microM. Low concentrations of both drugs caused marked stimulation of the energy dependent Ca2+ uptake. The extra Ca2+ taken up in the presence of the drugs was localized within the vacuoles, whereas K+ was lost mainly from the cytosolic pool. The ions Zn2+ and La3+ inhibited the effect of both drugs on the stimulation of Ca2+ uptake. The results indicated that both drugs caused an increase in the permeability of cell membranes to ions, leading to an increase in the influx of Ca2+ into the cytosol along its electrochemical gradient. Consequently, the concentration of Ca2+ within the cytosol increased and in turn led to the enhancement of Ca2+ uptake by the energy dependent vacuolar Ca2+ system, which functioned as a Ca2+ detoxification system.
Eilam
Y
Y
Lavi
H
H
Grossowicz
N
N
D001692:Biological Transport; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D004996:Ethidium / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007811:Lanthanum / Q000494:pharmacology; D008825:Miconazole / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D014617:Vacuoles / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology
D007811:Lanthanum; D008825:Miconazole; D006180:Proton-Translocating ATPases; D004996:Ethidium; D015032:Zinc; D011188:Potassium; D002118:Calcium