Membrane-Ordering Effects of Barbiturates on Pure Phospholipid Model Membranes

Intramolecular excimer formation of 1, 3-di(1-pyrenyl)propane (Py-3-Py) and fluorescence polarization of 1, 6-diphenyl-1, 3, 5-hexatriene (DPH) were used to investigate the effects of barbiturates on the fluidity of model membranes of phosphatidycholine (SPMVPC), phosphatidylserine (SPMVPS), and phosphatidylinositol (SPMVPI) fractions of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine cerebral cortex. In a dose-dependent manner, barbiturates decreased the excimer to monomer fluorescence intensity ratio (I'/I) of Py-3-Py and increased the anisotropy(r), rotational relaxation time (P), limiting anisotropy $(r_infty)$, and order parameter (S) of DPH in SPMVPC, SPMVPS and SPMVPI. This indicates that barbiturates decreased both the lateral and rotational diffusion of the probes in SPMVPC, SPMVPS and SPMVPI. The relative potencies of barbiturates in ordering the membranes were in the order: pentobarbital > hexobarbital > amobarbital > phenobarbital. This order correlates well with the anesthetic potencies of barbiturates and the potencies for enhancement of $\gamma$-aminobutyric acid-stimulated chloride uptake. Thus, it is strongly suggested that a close relationship might exist between the membrane ordering effects of barbiturates and the chloride fluxes across SPMV.