Instituto de Investigaciones Biológicas y Tecnológicas (IIBYT), CONICET-Cátedra de Química Biológica, Departamento de Química, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Córdoba, Argentina.
Colloids Surf B Biointerfaces. 2013 Jan 1;101:61-7. doi: 10.1016/j.colsurfb.2012.06.004. Epub 2012 Jun 15.
GABA(A) receptor is the main inhibitory receptor of the central nervous system. The phenols propofol and thymol have been shown to act on this receptor. GABA(A) is an intrinsic protein, the activity of which may be affected by physical changes in the membrane. Taking into account the lipophilicity of phenols, their interaction with the membrane and a consequent non-specific receptor modulation cannot be discarded. By using Langmuir films, we analyze the comparative effects on the molecular properties of the membrane exerted by propofol, thymol and other related compounds, the activities of which on the GABA(A) are under investigation in our laboratory. All the compounds were able to expand phospholipid films, by their incorporation into the monolayer being favored by less-packed structures. Nonetheless, they were able to be incorporated at lateral pressures above the equilibrium pressure estimated for a natural membrane. Epifluorescence images revealed their presence between phospholipid molecules, probably at the head-group region. Hence, all results indicated that the phenols studied were clearly able to interact with membranes, suggesting that their anesthetic activity could be the combined result of their interaction with specific receptor proteins and with their surrounding lipid molecules modulating the supramolecular organization of the receptor environment.
GABA(A) 受体是中枢神经系统的主要抑制性受体。已证明酚类化合物丙泊酚和百里酚作用于该受体。GABA(A) 是一种内在蛋白，其活性可能受到膜物理变化的影响。考虑到酚类的亲脂性，它们与膜的相互作用以及随之而来的非特异性受体调节不能被排除。通过使用 Langmuir 膜，我们分析了丙泊酚、百里酚和其他相关化合物对膜分子特性的比较影响，我们实验室正在研究它们对 GABA(A) 的活性。所有化合物都能够扩展磷脂膜，因为它们通过单层的掺入而被优先促进形成较少堆积的结构。尽管如此，它们仍能够在高于天然膜估计的平衡压力的侧向压力下被掺入。荧光显微镜图像显示它们存在于磷脂分子之间，可能位于头部基团区域。因此，所有结果表明，所研究的酚类化合物显然能够与膜相互作用，这表明它们的麻醉活性可能是它们与特定受体蛋白相互作用以及与其周围脂质分子调节受体环境的超分子组织的综合结果。
