Effects of Fipronil and surface behavior of neuronal insect and mammalian membranes

Abstract

The effects of Fipronil as well as the comparison between synaptosomal natural membranes (NMs) of mammal (NMBt) and insect (NMTi), that contain the ionotropic receptor GABA, was studied.This is the first report of biophysical studies of insect NMs and one of the first on the effects of Fipronil over membranes.Our result showed that NMTi appears to be more disordered than NMBt, generates more compressible films at the air-water interphase and they both showed a 2D transition in its compression isotherm. Each NM showed different lateral distribution and characteristic domain shapes when observed by DiI-C18 epifluorescence microscopy. Laurdan GP images suggested that in NMTi films, Ld and Ld-Lo phases are evenly abundant whereas in NMBt the Ld-Lo phase predominates. The differences observed might be attributed to differences in NMs lipid composition.The lipophilic insecticide Fipronil penetrated both NMs packed up to bilayer-compatible lateral pressures. The interface rearrangement after πt affected the interaction of Fipronil mainly in NMTi. The capability of the compound to be incorporated in expanded Langmuir films and remain when they are compressed was also observed. Fluorescence microscopy images suggest a disordering effect in NMTi while it ordered NMBt, showing that Fipronil affected the lateral distribution of lipids in NMs.We suggest that changes in order and lipid lateral organization caused by Fipronil might contribute to its mechanism of action.Our experiments evidenced that differences in the physical state of insect and mammal membranes become relevant for the design of new compounds with potential biological activity.