Effect of cetiedil on cation and water movements in erythrocytes

Cetiedil is a potential antisickling agent whose major effect appears to be at the erythrocyte membrane. To test the hypothesis that cetiedil alters cation transport, we studied the effect of the drug in promoting changes in cell water (Wc), cell sodium (Nac), and cell potassium (Kc). Results are quite different depending on the presence or near absence of intracellular ATP. With fresh cells, 100 microM cetiedil causes little in the net cation or water movements compared with control cells incubated for 2 h. At cetiedil concentrations greater than 100 microM, however, net movements of sodium and potassium increase considerably, and cell swelling results from a net Nac gain that exceeds a net Kc loss. All water movements can be accounted for by cetiedil-induced net cation movements. When 100 microM ouabain is added along with cetiedil, net Nac gain, net Kc loss, and net Wc gain are all increased compared with results obtained with cetiedil alone. External calcium inhibits cetiedil-induced changes in cation transport. With cells depleted of their ATP, cetiedil inhibits the typical potassium loss that occurs in the presence of external calcium; net sodium uptake changes little under these conditions, regardless of the presence or absence of external calcium. Our findings indicate a complex mode of action for cetiedil on the erythrocyte membrane, and support the hypothesis that the erythrocyte membrane, and support the hypothesis that the antisickling effect of the drug observed in vitro results from dilution of intracellular hemoglobin secondary to net salt and water gain.