An analysis of the mechanism by which cetiedil inhibits sickling

Abstract

A study has been carried out into the effects of cetiedil on the activities of Na+, K+ and Ca2+, Mg2+-ATPases of the normal human erythrocyte membrane. In general, cetiedil inhibits both ATPases activities but with characteristic inhibition profiles and varying degrees of efficacy. The activities were inhibited non-competitively at the cetiedil concentration which caused 50% inhibition of each enzyme. In addition, the effects of cetiedil on the transport of K+ and phosphate ions across the membrane were monitored and compared. Cetiedil was found to stimulate K+ release and to inhibit phosphate uptake. At low concentrations, both processes were concentration dependent. Stimulation of K+ efflux reached a plateau at a concentration of 1.2 mM. The antisickling effect of cetiedil is explained mainly in the light of the changes it induces in the activities of membrane-bound ATPases and the permeability properties of the erythrocyte membrane to cations and anions.