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

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 Ca2+-dependent K+-permability (‘Gardos effect’). The replacement of Cl− by NO3− 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.