The gabaergic insecticide Fipronil interacts with lipid membranes: a Langmuir film study

FELSZTYNA, IVÁN; SÁNCHEZ-BORZONE, MARIELA EUGENIA; GARCÍA, DANIEL ASMED

La Plata

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Biofísica; 2018

Sociedad Argentina de Biofísica

The GABAA receptor (GABA-R) is the main inhibitory receptor of the CentralNervous System and is a membrane intrinsic protein whose activity may beaffected by physical changes in the membrane. It possesses binding sites fordrugs other than the neurotransmitter GABA, including convulsant agents whichbehave as channel blockers. The latter constitutes the action site of widely used neurotoxic pesticides, including fipronil, an insecticide with low toxicity for humans. It was previously demonstrated that many lipophilic compounds thatregulate GABA-R function interact with membrane lipids causing changes in theirphysical properties and, consequently, non-specific receptor modulation cannot be discarded. Taking into account that the insecticide fipronil is highly lipophilic, we focused our study on its membrane interaction using dpPC monolayers. This work constitutes a part of a major project oriented to the development of bioinsecticides with high selectivity and low resistance. dpPC surface pressure versus area isotherms measured in the presence or absence of fipronil (0,25 to 25 μM in the subphase) showed that the insecticide was able to expand the LE phase of the phospholipidic interface in a concentration dependent manner, until the film saturation, diminishing the monolayer stability. The dpPC phase transition between LE and LC phases tends to disappear in the presence of fipronil. Compressibility modulus determination shows that all concentrations of fipronil modify the membrane elasticity. Furthermore, this compound can easily penetrate on the membrane according to their ability to incorporate into the monomolecular film at different surface pressures showing a πcutoff > 40 mN/m. These results suggest that the insecticidal activity of fipronil could involve the interaction, not only with GABA-R, but also with lipid molecules causing changes in the physical properties of the membrane.