Anthelmintic Actions of the Cyclic Depsipeptide PF1022A and its Electrophysiological Effects on Muscle Cells of Ascaris suum
✍ Scribed by Martin, Richard J.; Harder, Achim; Londershausen, Michael; Jeschke, Peter
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 606 KB
- Volume
- 48
- Category
- Article
- ISSN
- 1526-498X
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✦ Synopsis
The cyclic depsipeptide PF1022A, givea orally to mice, showed very good anthelmintic activity against Heligmosomoides polygyrus and Heterakis spwnosa at 50 mg kg-'. In uitro, PF1022A was very active against Trichinella spiralis and had good activity against Nippostrongylus brasiliensis at 1 pg d-'.
An 18-membered enniatin analogue, JES 1798, showed good activity only against N . brasiliensis at 10 pg d-'. The optical antipode of PF1022A had poor activity even at 100 pg d-l. The effects of PF1022A on the membrane potential and input conductance. of somatic muscle of Ascaris mum were examined using a two-microelectrode current-clamp technique. PF1022A did not antagonize the effects of the selective nicotinic agonist levamisole. PF1022A and an analogue, JES 1798, but not the PF1022A antipode, produced a small time-dependent increase in input conductance associated with no potential change. The increase in input conductance did not occur in the Cl--free bathing solution, suggesting that the increase in input conductance was mediated by C1-ions. The addition of high concentrations of Ca2+ to the preparation after the addition of PF1022A did not lead to production of CaZ +-activated C1-channels, suggesting that its mode of action was not that of a Ca2+ ionophore. The mechanism by which the cyclic depsipeptide might increase the C1-conductance is discussed.