Differential sensitivity of plant and yeast MRP (ABCC)-mediated organic anion transport processes towards sulfonylureas.
The role of ATP-binding cassette (ABC) proteins such as multidrug resistance-associated proteins (MRPs) is critical in drug resistance in cancer cells and in plant detoxification processes. Due to broad substrate spectra, specific modulators of these proteins are still lacking. Sulfonylureas such as glibenclamide are used to treat non-insulin-dependent diabetes since they bind to the sulfonylurea receptor. Glibenclamide also inhibits the cystic fibrosis transmembrane conductance regulator, p-glycoprotein in animals and guard cell ion channels in plants. To investigate whether this compound is a more general blocker of ABC transporters the sensitivity of ABC-type transport processes across the vacuolar membrane of plants and yeast towards glibenclamide was evaluated. Glibenclamide inhibits the ATP-dependent uptake of beta-estradiol 17-(beta-D-glucuronide), lucifer yellow CH, and (2',7'-bis-(2-carboxyethyl)-5-(and-6-)carboxyfluorescein. Transport of glutathione conjugates into plant but not into yeast vacuoles was drastically reduced by glibenclamide. Thus, irrespective of the homologies between plant, yeast and animal MRP transporters, specific features of plant vacuolar MRPs with regard to sensitivity towards sulfonylureas exist. Glibenclamide could be a useful tool to trap anionic fluorescent indicator dyes in the cytosol.
Forestier
Cyrille
C
CEA Cadarache, Direction des Sciences du Vivant, Département d'Ecophysiologie Végétale et de Microbiologie, Laboratoire des Echanges Membranaires et Signalisation, UMR 163 CNRS-CEA, F-13108, St Paul-lez-Durance, France.
Frangne
Nathalie
N
Eggmann
Thomas
T
Klein
Markus
M
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D005656:Fungal Proteins / Q000187:drug effects; D020719:Glucuronides / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors*; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors; D010940:Plant Proteins / Q000187:drug effects; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D064233:Sulfonylurea Receptors; D014617:Vacuoles / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate; D005456:Fluorescent Dyes; D005656:Fungal Proteins; D020719:Glucuronides; D005905:Glyburide; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027361:Organic Anion Transporters; D010940:Plant Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors