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Structure‐Specific Membrane‐Fluidizing Effect Of Propofol
Author(s) -
Tsuchiya H
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03441.x
Subject(s) - membrane , propofol , liposome , phosphatidylcholine , chemistry , lipophilicity , phospholipid , chromatography , biophysics , biochemistry , pharmacology , medicine , biology
SUMMARY 1. While recent studies about the pharmacological mechanism of the intravenous anaesthetic propofol (2,6‐diisopropylphenol) have focused on its interaction with functional proteins, there is the possibility that propofol alters membrane properties to produce anaesthesia. In the present study, the structure‐specific effects of propofol on liposomal model membranes were studied. 2. The effect of propofol on the phase transition of membrane phospholipid was analysed spectrophotometrically using 1,2‐dipalmitoyl‐ L ‐α‐phosphatidylcholine liposomes. Propofol (50–200 μmol/L) lowered the phase transition temperature to fluidize membranes. 3. Membrane fluidization was also analysed by measuring fluorescence polarization of liposomes consisting of 1,2‐ dipalmitoyl‐ L ‐α‐phosphatidylcholine, 1‐palmitoyl‐2‐oleoyl‐ L ‐ α‐phosphatidylcholine and cholesterol with different probes. Propofol fluidized all liposomal membranes in the concentration range 5–500 μmol/L by acting on both the inner and outer layers of the membranes. 4. The membrane effects of propofol were compared with those of 2,6‐dialkylphenols, 1,3‐dialkylbenzenes, 2‐alkylphenols and alkylbenzenes. Although the membrane‐fluidizing effects were shared by a series of structural analogues, propofol was most effective in fluidizing membranes, especially liposomal membranes consisting of 20 mol% cholesterol and 80 mol% 1‐palmitoyl‐2‐oleoyl‐ L ‐α‐phosphatidylcholine. 5. Lipophilicity was compared between propofol and its structural analogues using their capacity factors, determined by reverse‐phase high‐performance liquid chromatography. The potency of propofol to fluidize membranes was much greater than anticipated from its lipophilicity. 6. At 0.125–1.0 μmol/L, almost corresponding to clinically relevant concentrations, propofol significantly enhanced membrane fluidity of cholesterol‐containing 1‐palmitoyl‐2‐oleoyl‐ L ‐α‐phosphatidylcholine liposomes. 7. These results indicate that propofol fluidizes membranes in a structure‐specific manner through an interaction with membrane lipids. Such a membrane effect may be responsible for the mode of anaesthetic action of propofol.