Effect of GABAergic insecticide Fipronil on phospholipid monolayers

FELSZTYNA I; SÁNCHEZ M. E; GARCÍA D

La Plata

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

Sociedad Argentina de Biofísica.

he GABAA receptor (GABA-R) is the main inhibitory receptor of the Central Nervous System and is an instrinsic protein which activity may be affected by physical changes in membrane. It possesses binding sites for drugs other than the neurotransmitter GABA, including convulsant agents which behave as channel blockers. This last constitutes the action site of widely used neurotoxic pesticides, including fipronil, an insecticide with low toxicity for human. It was previously demonstrated that many lipophilic compounds that regulate GABA-R function interact with membrane lipids causing changes in their physical properties and, consequently, non-specific receptor modulation cannot be discarded. Taking into account that the insecticide fipronil is highly lipophilic, we focus on the membrane interaction study using phospholipidic monolayers of dpPC. This work constitutes a part from a major project oriented to the development of bioinsecticides with high selectivity and low resistence. Surface pressure versus area isotherms measured in the presence or absence of fipronil (XX to XX μM in the subphase) showed that the insecticide was able to expand the LE phase of the phospholipidic interfase 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 ketones modify the membrane elasticity. Furthermore, these compounds can easily penetrate on the membrane according to their ability to incorporate into the monomolecular film at different molecular pressures showing a πcutoff > 40 mN/m.