Effects of Gabaergic Phenols on Phospholipid Bilayers as Evaluated by ¹H-NMR

Gabriela N. Reiner, Leonardo Fernandes Fraceto, Eneida de Paula, María A. Perillo, Daniel A. García

Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, Brasil.
Departamento de Engenharia Ambiental, Universidade Estadual Paulista Júlio de Mesquita Filho, Sorocaba, Brasil.
Instituto de Investigaciones Biológicas y Tecnológicas (IIBYT), CONICET—Universidad Nacional de Córdoba, Córdoba, Argentina.

DOI: 10.4236/jbnb.2013.43A004                

Abstract

The phenols propofol and thymol, and lately carvacrol, eugenol and chlorothymol, have been shown to act as positive allosteric modulators on GABA_A receptor, which is the main inhibitory receptor of the central nervous system. GABA_A 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.

Keywords

Phenols; Propofol; GABA-A Receptor; Membrane Interaction; ¹H-RMN

Conflicts of Interest

The authors declare no conflicts of interest.

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