The kinetics of rhodamine 123 efflux from cells with multiple drug resistance under the action of energy metabolism inhibitors

: A study was made of the effects of inhibitors of ATP synthesis on the process of rhodamine 123 (R-123) release from sensitive sp2/0-Ag14 cells, multidrug-resistant mouse myeloma spEBR-5 cells and hybridoma IF7, derived from spEBR-5 cells. It has been shown that IF7 cells are cross-resistant to ethidium bromide, colchicine, actinomycin D and adriamycin. However, hybridoma IF7 cells, compared to parental spEBR-5 cells, show a lower resistance index. When studying the dependence of the R-123 efflux rate on glycolysis intensity (effect of 2 mM 2-deoxyglucose) and on the level of oxidative phosphorylation activity (effect of 2 mM KCN and 30 microM dinitrophenol), the following distinctive properties of the R-123 transport system of IF7 cells (compared to spEBR-5 cells) were detected: 1) uptake of R-123 into IF7 cells is similar to that observed for the sensitive sp2/0-Ag14 cells; 2) efflux of R-123 from IF7 cells takes place more intensely; 3) R-123 transport is dependent on the rate of glycolysis and may be inhibited by KCN. It is found that 2,4-dinitrophenol inhibits the R-123 efflux from all the cells. Verapamil reverses the multidrug resistance both in spEBR-5 and IF7 cells. The mechanisms of multidrug resistance of cells are discussed.