Abstract
The aim of this study was to provide a basis for examining the molecular mechanism for the pharmacological action of ethanol. We studied dinotmyristoylnotphosphatidylethanol (DMPEt)’s effects on specific locations of n-(9-anthroyloxy) palmitic acid or stearic acid (n-AS) within phosnotpholipids of synaptosomal plasma membrane vesicles isolated from bovine cerebral cortex (SPMV) and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from SPMV. DMPEt increased rotational mobility (increased disordering) of hydrocarbon interior, but it decreased mobility (increased ordering) of membrane interface, in native and model membranes. The degree of rotational mobility in accordance with the carbon atom numbers of phospholipids comprising neuronal membranes was in the order at the 16, 12, 9, 6 and 2 position of aliphatic chain present in phospholipids. The sensitivity of increasing or decreasing effect of rotational mobility of hydrocarbon interior or surface region by DMPEt differed depending on the neuronal and model membranes in the descending order of SPMV, SPMVPL and SPMVTL.
Highlights
The molecular mechanism of action of ethanol in the central nervous system (CNS) has long been a subject of great interest
The fluorescent anthroyloxy palmitate or stearate probes, 16-(9-anthroyloxy)palmitic acid (16-AP), 12-(9-anthroyloxy)stearic acid (12-AS), 9-(9anthroyloxy) stearic acid (9-AS), 6-(9-anthroyloxy) stearic acid (6-AS) and 2-(9-anthroyloxy)stearic acid (2-AS) were purchased from Molecular Probes, Inc. (Junction City, OR, USA). 1, 2-DMPC, phospholipase D, bovine serum albumin (BSA) and other reagents were obtained from Sigma
In the present study, using fluorescence probe technique, we examined the amphiphilic effects of DMPEt on the differential rotational mobility between interface and hydrocarbon interior of SPMV, SPMVTL and SPMVPL
Summary
The molecular mechanism of action of ethanol in the central nervous system (CNS) has long been a subject of great interest. We have recently shown that a pathway of ethanol metabolism with an unusual phospholipid, dimyristoylphosphatidylethanol (DMPEt) increased the bulk lateral and rotational mobilities, and annular lipid fluidity of neuronal membrane lipid bilayers, and had a greater fluidizing effect on the outer monolayer [17]. There is a good possibility that the effects of ethanol on the CNS result from a direct action on neuronal membranes and from the action of DMPEt [17]. The fluidity of the membrane outer monolayers may vary at different positions [18,19]
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