title: Alcohols are inhibitors of Saccharomyces cerevisiae multidrug-resistance pumps Pdr5p and Snq2p.
abstract: The effect of alcohols on cell membrane proteins has originally been assumed to be mediated by their primary action on membrane lipid matrix. Many studies carried out later on both animal and yeast cells have revealed that ethanol and other alcohols inhibit the functions of various membrane channels, receptors and solute transport proteins, and a direct interaction of alcohols with these membrane proteins has been proposed. Using our fluorescence diS-C3 (3) diagnostic assay for multidrug-resistance pump inhibitors in a set of isogenic yeast Pdr5p and Snq2p mutants, we found that n-alcohols (from ethanol to hexanol) variously affect the activity of both pumps. Beginning with propanol, these alcohols have an inhibitory effect that increases with increasing length of the alcohol acyl chain. While ethanol does not exert any inhibitory effect at any of the concentration used (up to 3%), hexanol exerts a strong inhibition at 0.1%. The alcohol-induced inhibition of MDR pumps was detected even in cells whose membrane functional and structural integrity were not compromised. This supports a notion that the inhibitory action does not necessarily involve only changes in the lipid matrix of the membrane but may entail a direct interaction of the alcohols with the pump proteins.
authors.affiliation: Faculty of Mathematics and Physics, Institute of Physics, Charles University, Prague 2, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Gášková
authors.forename: Jaromír
authors.initials: J
authors.lastname: Plášek
authors.forename: Jakub
authors.initials: J
authors.lastname: Zahumenský
authors.forename: Ivana
authors.initials: I
authors.lastname: Benešová
authors.forename: Luboslava
authors.initials: L
authors.lastname: Buriánková
authors.forename: Karel
authors.initials: K
authors.lastname: Sigler
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000438:Alcohols / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D025141:Drug Resistance, Fungal / Q000235:genetics; D007477:Ions / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D000438:Alcohols; D007477:Ions; C092438:PDR5 protein, S cerevisiae; C101797:SNQ2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate
keywords: alcohols; fluorescent probe diS-C3(3); membrane potential; pump inhibitor; yeast MDR pump