| Abstract: | PF 1022A, a 24-membered cyclooctadepsipeptide and a potent anthelmintic drug, is active against nematodes but not against arthropods. Muscle cells of Ascaris suum generate autorhythmic spikes in electrophysiological control experiments. Exposure of the worm to PF 1022A leads to flaccid paralysis and in parallel to the disappearance of these spike events. Results of such experiments in vitro were compared with those from experiments using planar lipid bilayer membranes incorporating PF 1022A, a related linear octadepsipeptide and other cyclodepsipeptides. Whereas PF 1022A acts both as an ionophore in lipid bilayers, similar to other cyclodepsipeptides like valinomycin and enniatin A, and as a paralysing drug in worms, some of the series of depsipeptides examined have only an ion carrier function, while others exhibit only nematocidal activity. It is concluded that the ion carrier property of PF 1022A is not responsible for its paralyzing effect on nematodes and that there is a specific binding site for PF 1022A in nematodes. Binding may trigger the lethal reaction cascade, which is responsible for anthelmintic activity. |
