Effect of thujone and dihydrocarvone on phospholipid monolayer

MARIANI, ELISA; MARIELA SÁNCHEZ; DANIEL GARCÍA

Santiago del Estero

Congreso; XLIV Reunion Anual de la Sociedad Argentina de Biofisica (SAB).; 2015

Sociedad Argentina de Biofísica

The GABAA receptor (GABA-R) is the main inhibitory receptor of the Central Nervous System. It possesses binding sites for drugs other than the neurotransmitter GABA, including benzodiazepines, barbiturates, and the convulsant picrotoxine which behave as allosteric modulators or channel blockers. The study of this last site is especially relevant since it constitutes the action site of widely used neurotoxic organochlorine pesticides. Our group has studied some cyclic ketones, structurally similar to the convulsant product thujone, demonstrating their ability to inhibit the GABA-R activity. Many compounds that regulate GABA-R function are noticeably lipophilic, which can interact with membrane lipids and cause various changes of the physical properties (molecular area, surface tension, surface potential, etc) which in turn would result in changes in membrane dynamic properties (Fluidity, viscosity, etc) and can modulate receptor macromolecules. Taking into account that both ketones (thujone, the reference compound and dyhidrocarvone which shows to be very similar structurally) studied in the present work are highly lipophilic, we focus on the interaction study using Langmuir monolayers of DPPC. Surface pressure versus area isotherms measured at 22-25°C in the presence or absence of 20, 250 and 500 μM ketones in the subfase were determined. The results showed differences in the area occupied by the DPPC monolayer: while thujone compress the monolayer, dyhidrocarbone expanded it. Moreover, the data obtained by determination of the compressibility modulus, shows that all ketones are able to modify the membrane fluidity. Furthermore, this compounds shows to self penetrate lipid monolayers by their incorporation into the monomolecular film causing an increment in surface pressure and this way changes in the physical environment of the receptor. Acknowledgements:This work was supported by grants from SECyT-UNC, FONCYT-MinCyT and CONICET, Argentina.