Erythrocyte G Protein as a Novel Target for Malarial Chemotherapy
Figure 5
β-Blockers Inhibit Maturation of P. falciparum in In Vitro Cultures
(A) [3H]-hypoxanthine incorporation of P. falciparum 3D7 when treated with racemic propranolol (indicated by black diamonds) or its inactive isomer (indicated by grey squares). Error bars show the standard deviation of triplicate measurements. IC50 values were determined by fitting the data as described in Methods; the IC50 value obtained for racemic propranolol (1.2 μM; 95% CI 1.0–1.6 μM) is shown. Three experiments; hatched sign indicates p < 0.001; asterisks indicate p < 0.03 compared to equimolar inactive propranolol.
(B) Effect of 2 μM propranolol on intracellular growth in normal erythrocytes. Mock- and drug-treated cultures were monitored at 15, 32, and 44 h after invasion by examination of Giemsa-stained thin blood smears. The number of ring (R)–, trophozoite (T)–, and schizont (S)–stage parasites per 1,000 total erythrocytes at each time point are shown; numbers in parentheses indicate the standard deviation of triplicate measurements from one experiment; the total number of experiments was three.
(C) [3H]-hypoxanthine incorporation of P. falciparum 3D7–infected erythrocytes treated with 1 or 10 μM concentrations of adrenergic-acting drugs (nonspecific β1/β2–antagonists: propranolol, alprenolol, and nadolol; β2-specific antagonists: ICI118,551 and butoxamine; β1-specific antagonists: acebutalol, atenolol, and metoprolol; and α2-specific agonist [ag]: clonidine). Chloroquine (50 nM) was used as an inhibitory control. Triplicate samples; asterisks denote a treatment with p < 0.001 compared to control-treated cultures.