Pyrethroid stimulation of ion transport across frog skin

Pyrethroids are grouped into two classes (types I and II) because of the absence or presence of an alpha-cyano substituent and the production of a different intoxication syndrome in rodents. In this study, we investigated the effect of pyrethroids on the ion transport across frog skin (Rana esculenta). The short-circuit current value (estimate of ion transport) was increased by each of the eight pyrethroids tested, with the following order of potency: lambda-cyhalothrin > deltamethrin > alpha-cypermethrin = beta-cyfluthrin > bioallethrin > permethrin > bioresmethrin > phenothrin. The first four compounds are type II pyrethroids. Therefore, ion transport is stimulated more by type II pyrethroids than by type I. Experiments performed in the presence of amiloride support the conclusion that pyrethroids mainly increase Na+ absorption and to a lesser extent Cl- secretion. In these experiments, no systematic difference between type I and II pyrethroids was found. Finally, the stimulation by pyrethroids was inhibited by indomethacin and W7 (inhibitors of cyclooxygenases and the Ca2+/calmodulin system, respectively). These observations suggest that pyrethroids do not directly affect the epithelial Na+ channel (ENaC) but indirectly influence an intracellular event involved in ENaC modulation and linked to the Ca2+ signaling cascade.