title: The inhibition of ATP-dependent shape change of human erythrocyte ghosts correlates with an inhibition of Mg(2+)-ATPase activity by fluoride and aluminofluoride complexes.
abstract: The vanadate-sensitive Mg(2+)-dependent ATPase activity of the human erythrocyte ghost is believed to be involved in the shape change events that convert echinocytic ghosts to smoothed forms (biconcave discs and stomatocytes). At physiological salt concentration, pH 7.4, 2 mM ATP, 5 mM Mg2+ and 1 mM EGTA, the Mg(2+)-ATPase activity of ghosts was inhibited strongly by millimolar concentrations of sodium fluoride: I50 = 1.31 +/- 0.23 mM (mean +/- S.D.; n = 12). The addition of aluminium chloride to 15 microM reduced the concentration of NaF required for 50% inhibition to 0.76 +/- 0.21 mM (n = 10). Aluminium alone had only a small inhibitory effect on the ATPase activity (13 +/- 9%; n = 10). Desferrioxamine, a strong chelator of tervalent aluminium ion, failed to reverse the inhibition by fluoride and reversed the inhibition in the presence of aluminium and fluoride back to those values obtained with fluoride alone. Of several metal salts tested only beryllium sulfate was able to replace aluminium as an effective inhibitor in the presence of fluoride. Inhibition of the Mg(2+)-ATPase activity by fluoride and the aluminofluoride complexes correlated with an inhibition of the rate of MgATP-dependent change in red cell ghost shape from echinocytes to smoothed forms. All gross morphological changes of the smoothing process were affected, including the production of discocytes, stomatocytes and endocyctic vesicles.
authors.affiliation: Department of Pharmacy, University of Sydney, Australia.
authors.forename: M B
authors.initials: MB
authors.lastname: Morris
authors.forename: G
authors.initials: G
authors.lastname: Monteith
authors.forename: B D
authors.initials: BD
authors.lastname: Roufogalis
mesh_terms: D000535:Aluminum / Q000494:pharmacology*; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology*; D005459:Fluorides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques
chemical_list: D000535:Aluminum; D017301:Ca(2+) Mg(2+)-ATPase; D005459:Fluorides