Gangliosides enhance the membrane actions of ethanol and pentobarbital

R. A. Harris, G. I. Groh, D. M. Baxter, R. J. Hitzemann

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

The physical properties of vesicles containing phosphatidylcholine (PC) and gangliosides were evaluated by the fluorescent probes 1,6-diphenyl-1,3,5-hexatriene, trans-parinarate (probes of the lower acyl regions), and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (a probe of the glycerol backbone and upper acyl regions). Exposure of PC vesicles to ethanol produced a decrease in polarization of fluorescence of these probes, but large concentrations (200-600 mM) were required. Incorporation of 10 mole% rat brain synaptic gangliosides into the PC vesicles enhanced the effect of ethanol by several-fold. Synaptic gangliosides also enhanced the effect of ethanol on vesicles containing cholesterol in addition to PC. Comparison of mono-, di-, tri-, and asialogangliosides, sphingosine, and sphingomyelin indicated the importance of the oligosaccharide moiety, but not the sialic acid residues, in the enhancement of ethanol action by gangliosides. Variation of assay temperature and the acyl composition of the PC demonstrated that gangliosides increased the effects of ethanol only if the lipids were near the phase transition temperature. Gangliosides also produced a marked enhancement of the effect of pentobarbital on fluorescence polarization of probes in PC vesicles. The membrane partioning of pentobarbital was increased by gangliosides, but it was not clear that this increase in drug concentration in the membrane was sufficient to account for the large change in fluorescence polarization. These results suggest that ganglioside content may be an important determinant of the effects of alcohols and barbiturates on biomembranes. In particular, the high drug sensitivity of neuronal membranes may be related to the enrichment of gangliosides in these membranes.

Original languageEnglish (US)
Pages (from-to)410-417
Number of pages8
JournalMolecular pharmacology
Volume25
Issue number3
StatePublished - Jan 1 1984

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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