Cytochalasin D abolishes the schistosomicidal activity of praziquantel

• Published in: Experimental parasitology Vol. 115; no. 4; pp. 344 - 351
• Main Authors: Pica-Mattoccia, Livia, Valle, Cristiana, Basso, Annalisa, Troiani, Anna Rita, Vigorosi, Fabio, Liberti, Piero, Festucci, Alfredo, Cioli, Donato
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.04.2007; Elsevier
• Subjects: Actin cytoskeleton; Actins - drug effects; Animals; Biological and medical sciences; Biomphalaria; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Calcium blockers; Calcium Channel Blockers - pharmacology; Calcium channels; Calcium Channels - drug effects; Cytochalasin D; Cytochalasin D - pharmacology; Cytoskeleton - drug effects; Fundamental and applied biological sciences. Psychology; Life cycle. Host-agent relationship. Pathogenesis; Male; Mice; Nucleic Acid Synthesis Inhibitors - pharmacology; Parasitic Sensitivity Tests; Praziquantel; Praziquantel - pharmacology; Protozoa; Schistosoma mansoni; Schistosoma mansoni - drug effects; Schistosomicides - pharmacology; Thiazolidines - pharmacology; Trematode; Schistosoma mansoni; Calcium channels; Praziquantel; Calcium blockers; Cytochalasin D; Trematode; Actin cytoskeleton; Parasite; Activity; Cytochalasin
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2006.09.017

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 μM) 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 μM). These results are consistent with the hypothesis that schistosome calcium channels are involved in the mechanism of action of praziquantel.