Potassium chloride cotransport in steady-state ascites tumor cells. Does bumetanide inhibit?
Bumetanide is a potent diuretic drug which has some structural features in common with furosemide. The steady-state exchange of K+ and Cl- was investigated in Ehrlich ascites tumor cells treated with bumetanide. This agent did not alter the cellular content of K+ or Cl- but the self-exchange of both ions was depressed. K+ self-exchange was inhibited by 55% at bumetanide concentrations as low as 10(-6) M. Cl- self-exchange was less sensitive to this drug but at low concentrations (between 10(-6) and 10(-3) M) bumetanide was a more effective inhibitor of Cl- transfer than furosemide. The steady-state K+ flux of cells equilibrated in NO3- media was compared with the K+ flux in cells treated with 10(-4) or 10(-3) M bumetanide; the Cl(-)-sensitive K+ exchange was equivalent to the bumetanide-sensitive K+ exchange. Since the results suggested that a bumetanide-sensitive (Cl-, K+) cotransport could be operative in steady-state cells, the stoichiometry of the bumetanide-sensitive fluxes was determined by measuring Cl- and K+ fluxes simultaneously in the same cell suspension. At 5 . 10(-4) and 10(-3) M bumetanide concentrations, the ratio of these fluxes was 0.98 +/- 0.07 (S.E.) and 1.04 +/- 0.06, respectively, consistent with the postulated cotransport mechanism. At 10(-4) and 10(-5) M, however, the ratio of the bumetanide-sensitive Cl-/K+ flux was significantly less than 1.0. Since the magnitude of the bumetanide-sensitive K+ flux at 10(-4) M was close to that of the Cl(-)-sensitive flux, a ratio of less than 1.0 at this drug level indicates that Cl-sensitivity and drug sensitivity may not reflect inhibition of the same process under all circumstances.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism* / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D011188:Potassium / Q000378:metabolism*; D011189:Potassium Chloride / Q000378:metabolism*
D002712:Chlorides; D004232:Diuretics; D002034:Bumetanide; D011189:Potassium Chloride; D011188:Potassium