Stimulation of K+ fluxes by diuretic drugs in human red cells.

Abstract Two different families of diuretic drugs—(i) (aryloxy)acetic acid diuretics (ethacrynic acid, tienilic acid and (−)-indacrinone) and (ii) furopyridines [(±)-BN 50157 and (±)-cycletanide]—stimulate K + movements across human red cell membranes. The kinetic properties of this effect (K + -specificity, saturability, optical isomerism, antagonism by structural analogues, etc.) strongly suggest that it is mediated by a K + -transport system with a specific binding site for some diuretic drugs. The stimulated K + fluxes are resistant to ouabain, bumetanide and quinine, thus suggesting that they are not mediated by the Na + , K + -pump, Na + , K + -cotransport or by the Ca 2+ -dependent K + -permability (‘Gardos effect’). The replacement of Cl − by NO 3 − ions can either decrease, increase or have no effect on the stimulated K + fluxes, depending on the diuretic drug. Although not conclusive, these observations suggest that the K + fluxes are not mediated by stimulation of a chloride-dependent K + carrier. The study of structural analogues showed that the intensity of the stimulation of K + fluxes is strongly correlated with the magnitude of the natriuretic effect. Curiously, some antiallergic furopyridines are able to inhibit K + fluxes.