Effects of cetiedil on monovalent cation permeability in the erythrocyte: an explanation for the efficacy of cetiedil in the treatment of sickle cell anemia.
Cetiedil, a drug reported to relieve painful crises in sickle cell anemia, has direct antisickling properties in vitro. However, neither oxygen affinity nor the solubility of deoxyhemoglobin S is altered by cetiedil. Due to the great influence the concentration of hemoglobin S has on the kinetics of gelation, we hypothesized that cetiedil might inhibit sickling by modifying erythrocyte Na+ or K+ movements in a manner which would prevent a rise in the concentration of intracellular hemoglobin. Cetiedil has two such effects: It causes a rise in passive Na+ movements and it inhibits a specific increase in K+ permeability secondary to a rise in cytoplasmic Ca2+ concentration. Cetiedil then may represent an alternate type of antisickling agent, exerting its effect through changes in erythrocyte membrane cation permeability rather than directly modifying hemoglobin S.
D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy*; D000986:Antisickling Agents / Q000494:pharmacology / Q000627:therapeutic use; D001381:Azepines / Q000494:pharmacology* / Q000627:therapeutic use; D002414:Cations, Monovalent; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004913:Erythrocytes, Abnormal / Q000378:metabolism*; D006801:Humans; D010100:Oxygen / Q000097:blood; D012964:Sodium / Q000097:blood
D000986:Antisickling Agents; D001381:Azepines; D002414:Cations, Monovalent; C006955:cetiedil; D012964:Sodium; D010100:Oxygen