An effect of piretanide upon the intracellular cation contents of cells subjected to partial chronic (Na-K) pump blockade by ouabain.
Cultured cells have been used to study the contribution made by the ouabain-insensitive but diuretic (piretanide)-sensitive K transport system (so-called cotransport) to the maintenance of intracellular Na+ and K+ contents in normal cells and in cells whose Na-pump sites have been subjected to chronic partial inhibition. In cells which have normally directed gradients of Na+ and K+, chronic incubation in piretanide (10(-4) M) for up to 24 hr has no significant effect on the internal ion contents of HeLa (human carcinoma), MDCK (dog kidney epithelium) or BC3H1 (mouse smooth muscle) cell lines. This observation is consistent with the notion that when the intracellular ion contents are in a normal steady state the net driving force acting upon the diuretic-sensitive K transport (Na + K + Cl cotransport system) is zero or very close to zero. When cells are subjected to chronic partial inhibition of the sodium pump as a consequence of growth in sublethal concentrations of ouabain (10(-9)-3 X 10(-7) M), the number of functional Na-pump sites decreases, the intracellular Na+ content increases and the intracellular K+ decreases in a dose dependent manner. Under these conditions, inclusion of piretanide (10(-4) M) causes a significant retardation of Na+ gain and K+ loss from the cells. This response is of high molar affinity (EC50 = 3-4 X 10(-6) M) and can be obtained with the other loop diuretics, furosemide and bumetanide. The data presented are consistent with the idea that in cells subjected to chronic partial inhibition of the Na-pump, there is a piretanide-sensitive exchange of intracellular K+ for extracellular Na+. Such an effect of the cotransport system would not be predicted on the basis of a tightly coupled electroneutral cotransport of Na+, K+ and Cl- with a stoichiometry of 1Na:1K:2Cl. The data are discussed in relation to the possible role of putative circulating endogenous inhibitors of the Na-pump.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D004232:Diuretics / Q000494:pharmacology*; D004285:Dogs; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D051379:Mice; D009130:Muscle, Smooth / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*
D004232:Diuretics; D013449:Sulfonamides; D010042:Ouabain; D012964:Sodium; C015451:piretanide; D011188:Potassium