Effects of gabaergic phenols on phospholipid bilayers evaluated by 1H-RMN

REINER GN; FRACETO LF; DE PAULA E.; PERILLO MA; GARCÍA DA

Buzios, Rio de Janeiro,

Congreso; II Latinamerican Federetion of Biophysical Societies (LAFeBS); 2012

The GABAA receptor (GABA-R), a ligand-gated ion channel, constitutes the main inhibitory receptor of the central nervous system. The GABA-R ligands include drugs other than the GABA neurotransmitter, such as benzodiazepines, barbiturates, anesthetics, neurosteroids and ethanol. The phenols propofol and thymol, and recently carvacrol, eugenol and chlorothymol, have been shown to act on this receptor as positive allosteric modulators. GABA-R is a membrane intrinsic protein whose activity may be affected by surface-active compounds and by physical changes in the membrane. Thus, given the lipophilicity of these phenol compounds, their interaction with the membrane region surrounding the receptor and a consequent non-specific receptor modulation cannot be discarded. In the present work we analyze the insertion ability and effects of these five phenol derivatives with GABAergic activity on the Egg-PC membranes by using 1H-NMR spectroscopy.  Spectra 1H-NMR of each compound, of Egg-PC liposomes and of Egg-PC liposomes in the presence of each phenol were collected and chemical shifts (C.S.) and longitudinal relaxation times (T1) were calculated. All compounds were capable to insert in the membrane withing the region occupied by the polar head groups and glycerol backbones of phospholipid molecules, according to their hydrophobicity. This location would induce a decrease in the polar head repulsion, reduces the intermolecular spacing thus impairing of molecular movements within different zones of the acyl chain. Acknowledgments: Capes, Fapesp, CNPq, LNLS, Conicet, Secyt-UNC, Foncyt.