The efflux of Rhodamine-123 (R-123) and of anions (125I-) from a P-glycoprotein expressing ovarian cell line are mutually independent
P-glycoprotein expression causes the phenomenon of multiple drug resistance in tumour cells but it has been suggested that the protein may also mediate the increase in anion conductance that accompanies cell swelling. Support for this came from the observation that cell swelling inhibits the efflux of P-gp substrates, and that such substances reduce the swelling-evoked rise in anion conductance. However, hypotonic external solutions did not influence the rate at which a fluorescent, P-glycoprotein substrate, R-123, was exported from P-glycoprotein ovarian adenocarcinoma cells (A2780.ad) although this efflux was blocked by the P-gp inhibitor verapamil (30 μM) confirming the involvement of P-gp. In further experiments, we monitored anion permeability by measuring 125I- efflux. Cells were loaded with 125I- both under control conditions and in the presence of R-123 so that we could quantify anion efflux from control cells and from cells that were exporting R-123. The half times for 125I--efflux measured under these conditions (control: 6.4 ± 0.4 min; R-123-exporting; 6.2 ± 0.2 min, N = 4 paired experiments) were identical. Moreover, hypotonic shock evoked an essentially identical 125I--efflux from both groups of cells (control: 0.168 ± 0.016 min-1 R-123-exporting: 0.136 ± 0.048 min-1, N = 11 paired experiments). R-123 efflux and anion efflux thus appear to be mutually independent in A2780.ad cells.