IIBYT   23944
INSTITUTO DE INVESTIGACIONES BIOLOGICAS Y TECNOLOGICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
EFFECT OF THUJONE AND DIHYDROCARVONE ON PHOSPHOLIPID MONOLAYER
Autor/es:
M.E MARIANI; MARIELA SANCHEZ-BORZONE; DANIEL A. GARCIA
Lugar:
Córdoba
Reunión:
Otro; IV Reunión Científica Anual del IIByT; 2016
Institución organizadora:
IIByT
Resumen:
The GABAA receptor (GABA-R) is the main inhibitory receptor of the Central NervousSystem. It possesses binding sites for drugs other than the neurotransmitter GABA, includingbenzodiazepines, barbiturates, and the convulsant picrotoxine which behave as allostericmodulators or channel blockers. The study of this last site is especially relevant since itconstitutes the action site of widely used neurotoxic organochlorine pesticides. Our group hasstudied 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 interactwith 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 membranedynamic properties (Fluidity, viscosity, etc) and can modulate receptor macromolecules.Taking into account that both ketones (thujone, the reference compound and dyhidrocarvonewhich 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 pressureversus area isotherms measured at 22-25°C in the presence or absence of 20, 250 and 500 μMketones in the subfase were determined. The results showed differences in the area occupied bythe DPPC monolayer: while thujone compress the monolayer, dyhidrocarbone expanded it.Moreover, the data obtained by determination of the compressibility modulus, shows that allketones are able to modify the membrane fluidity. Furthermore, this compounds shows to selfpenetrate lipid monolayers by their incorporation into the monomolecular film causing anincrement in surface pressure and this way changes in the physical environment of the receptor.