An analysis of the mechanism by which cetiedil inhibits sickling.
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.
Abu-Salah
Khalid M
KM
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
Gambo
Al-Hafiz A
AH
D000755:Anemia, Sickle Cell / Q000188:drug therapy*; D000986:Antisickling Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques
D000986:Antisickling Agents; D001381:Azepines; D027682:Cation Transport Proteins; C006955:cetiedil