Inhibition of erythrocyte calcium transport by cetiedil.
The elevated calcium content found in red cells from patients with sickle cell anemia may be of pathophysiologic importance in the hemolysis and vasoocclusion which characterize this disorder. Cetiedil, an antisickling agent, has been reported to inhibit the activity of enzymes that are stimulated by the calcium regulatory protein calmodulin. To investigate the mechanism by which cetiedil modifies calcium-mediated erythrocyte function, the effect of the drug on the active transport of calcium into inside-out erythrocyte vesicles was examined and its influence on the activities of phosphodiesterase and Ca-ATPase studied. Cetiedil, in the presence of calmodulin, significantly inhibited calcium transport into inside-out vesicles that were prepared with erythrocytes from normal controls and from patients with sickle cell anemia. However, in the absence of calmodulin, no inhibition was observed. Likewise, cetiedil inhibited calmodulin-stimulated, but not basal, activities of phosphodiesterase and Ca-ATPase. These data, along with previous reports, suggest that cetiedil does not act by lowering the intracellular calcium content. It is, therefore, likely that the beneficial effect of cetiedil is due to its ability to protect the red cell from the deleterious consequences of an elevated concentration of intracellular calcium.
Levine
S N
SN
Department of Medicine, Louisiana State University Medical Center, Shreveport.
Berkowitz
L R
LR
Orringer
E P
EP
D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy; D000986:Antisickling Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000097:blood*; D000252:Calcium-Transporting ATPases / Q000097:blood; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010727:Phosphoric Diester Hydrolases / Q000097:blood
D000986:Antisickling Agents; D001381:Azepines; C006955:cetiedil; D010727:Phosphoric Diester Hydrolases; D000252:Calcium-Transporting ATPases; D002118:Calcium