Membrane dipolar organization modulates [3H]FNTZ binding to GABAA receptor

TURINA A; SÁNCHEZ M; GARCÍA D; PERILLO M.A

Buenos Aires,

Congreso; XIV International Biophysics Congress; 2002

Sociedad Argentina de Biofísica

Thymol self-aggregated in aqueous media with a c.m.c.=0.00062M. It penetrated monomolecular layers at the air-water interface up to 32.98 mN/m, increased Triton X-100´s cmc value from 1.3x10-4M to 6.2x10-4M, increased the curvature of dpPC bilayers and increased the polarity of its environment in a membrane. A dipole moment of 1,341 D was calculated from its energy minimized structure. Thymol´s effect on [3H]flunitrazepam (FNTZ) binding changed from  inhibitory to activatory up on changing from monomer to self-aggregated. Above its c.m.c., it increased the affinity of [3H]FNTZ binding to synaptosomal membranes from chick forebrain (Kd,control= 2.9±0.2 nM and Kd,thymol =1.7± 0.1 nM) without changing the receptor density (Bmax-control-= 910±100 and Bmax-timol-= 895±81 ¦mol/mg protein). The activatory effect of thymol on FNTZ binding was observed even in the presence of a maximal activatory GABA concentrations. Bicuculine blocked thymol’s ability to stimulate [3H]FNTZ binding. Our results suggest that thymol: I-locates at the polar head group membrane region, with its dipole moment oriented parallel to the intrinsic  membrane dipole vectors; II- thymol-induced allosteric activation of [3H]FNTZ binding, may involved changes in the dipolar environment of GABAA receptor in addition to thymol binding to GABA receptor.