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 mu M) 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 mu M). These results are consistent with the hypothesis that schistosome calcium channels are involved in the mechanism of action of praziquantel. (c) 2006 Elsevier Inc. All rights reserved.