title: Inhibition of calmodulin stimulation of phosphodiesterase and Ca2+, Mg2+-ATPase activities and shape change of erythrocyte ghosts by chloroquine.
abstract: The effects of chloroquine on calmodulin (CaM)-related enzyme activities and the shape of human erythrocytes have been studied. It was found that the CaM activation of rat brain phosphodiesterase was abolished by the addition of chloroquine. CaM was included in the assay of phosphodiesterase activity at the concentration that gave half-maximal activation. The concentration of chloroquine that caused 50% inhibition of CaM stimulation of phosphodiesterase was 7 X 10(-5)M. The type of inhibition was competitive with respect to CaM. The CaM-stimulated Ca2+, Mg2+-ATPase in erythrocyte membrane was also inhibited by chloroquine, the 50% inhibitory concentration of which was about 2 X 10(-4)M. Its mode of action was also competitive with respect to CaM. The shapes of erythrocyte ghosts prepared by hypotonic hemolysis were examined in a solution consisting of 2 mM MgCl2, 154 mM NaCl and 10 mM Tris-HCl (pH 7.4); they were discocytic in the presence of 2 mM ATP and in its absence. They were converted to the invaginated form by the addition of chloroquine in the concentration range of 1 X 10(-4)-5 X 10(-4)M. This concentration is similar to that which caused the inhibition of CaM activation of Ca2+, Mg2+-ATPase.
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002417:Cattle; D002738:Chloroquine / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*
chemical_list: D002147:Calmodulin; D010726:Phosphodiesterase Inhibitors; D002738:Chloroquine; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases