Effects of Gabaergic phenols on phospholipid bilayers as evaluated by 1H.NMR.

GABRIELA N. REINER; DANIEL A. GARCÍA; ENEIDA DE PAULA; LEONARDO F. FRACETO; MAR

Journal of Biomaterials and Nanobiotechnology

Scientific Research Publishing

Lugar: Delaware; Año: 2013

2158-7027

The phenols propofol and thymol, and recently carvacrol, eugenol and chlorothymol, have been shown to act as positive allosteric modulators on GABAA receptor, the main inhibitory receptor of the central nervous system. GABAA receptor is an intrinsic membrane protein which activity may be affected by surface-active compounds and by physical changes in the membrane. Recently, we demonstrated that these phenols interact with the lipid membrane phase, suggesting their anesthetic activity could be the combined result of their specific (with receptor proteins) as well as nonspecific (with surrounding lipid molecules) interaction modulating the supramolecular organization of the receptor environment. In the current study, by using 1H-NMR spectroscopy, we have investigated the effects of the insertion and the possible preferential location of the five phenol derivatives with GABAergic activity on EPC membranes. The results indicated that all compounds are able to insert in EPC phospholipid vesicles and to locate in the region between the polar group (choline molecule), the glycerol and the first atoms of the acyl chains, being the more lipophilic compounds (propofol and chlorothymol) those that seems to prefer a deeper bilayer insertion. The location of the phenol molecules would reduce the repulsive forces among phospholipids head groups allowing closer molecular packing and finally diminishing the mobility of the hydrocarbon chains, as revealed by 1H spin relaxation times.