Cytochalasin D abolishes the schistosomicidal activity of praziquantel.
To test the hypothesis that calcium channels of schistosomes are the targets for the action of praziquantel, we subjected schistosomes in vitro to pharmacological agents capable of interfering with the functioning of calcium channels. After 1-h exposure to these agents, praziquantel was added and incubation continued overnight. Worms were then washed, resuspended in drug-free medium and observed during the following 7-10 days. About 50% of schistosomes pre-exposed to the calcium channel blockers nicardipine and nifedipine were able to survive a praziquantel concentration (3 microM) that normally killed the majority of adult male worms. Since the organization of the actin cytoskeleton controls the activity of calcium channels in a number of different systems, we also pre-exposed schistosomes to the actin depolymerizing agent cytochalasin D. This treatment rendered the parasites completely refractory to the effects of very high praziquantel levels (up to 36 microM). These results are consistent with the hypothesis that schistosome calcium channels are involved in the mechanism of action of praziquantel.
Pica-Mattoccia
Livia
L
Institute of Cell Biology, National Research Council, Monterotondo, Rome, Italy.
Valle
Cristiana
C
Basso
Annalisa
A
Troiani
Anna Rita
AR
Vigorosi
Fabio
F
Liberti
Piero
P
Festucci
Alfredo
A
Cioli
Donato
D
D000199:Actins / Q000187:drug effects; D000818:Animals; D001700:Biomphalaria; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D015638:Cytochalasin D / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects; D008297:Male; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D011223:Praziquantel / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects*; D012556:Schistosomicides / Q000494:pharmacology*; D053778:Thiazolidines / Q000494:pharmacology
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D019384:Nucleic Acid Synthesis Inhibitors; D012556:Schistosomicides; D053778:Thiazolidines; D015638:Cytochalasin D; D011223:Praziquantel; C037067:latrunculin A