TITLE:
Effects of Gabaergic Phenols on Phospholipid Bilayers as Evaluated by 1H-NMR
AUTHORS:
Gabriela N. Reiner, Leonardo Fernandes Fraceto, Eneida de Paula, María A. Perillo, Daniel A. García
KEYWORDS:
Phenols; Propofol; GABA-A Receptor; Membrane Interaction; 1H-RMN
JOURNAL NAME:
Journal of Biomaterials and Nanobiotechnology,
Vol.4 No.3A,
June
26,
2013
ABSTRACT: The phenols
propofol and thymol, and lately carvacrol, eugenol and chlorothymol, have been
shown to act as positive allosteric modulators on GABAA receptor, which is 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 interacted 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 indicate 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) that
seem 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.