Structure-Specific Membrane-Fluidizing Effect Of Propofol

Author: Tsuchiya H.

Source: Clinical and Experimental Pharmacology and Physiology, Volume 28, Number 4, April 2001 , pp. 292-299(8)

Publisher: Wiley-Blackwell

Abstract:

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--phosphatidylcholine liposomes. Propofol (50–200 mol/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--phosphatidylcholine, 1-palmitoyl-2-oleoyl-L- -phosphatidylcholine and cholesterol with different probes. Propofol fluidized all liposomal membranes in the concentration range 5–500 mol/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--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 mol/L, almost corresponding to clinically relevant concentrations, propofol significantly enhanced membrane fluidity of cholesterol-containing 1-palmitoyl-2-oleoyl-L--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.

Keywords: fluorescence polarization; membrane fluidity; phase transition; propofol; structure specificity

Language: English

Document Type: Research article

Publication date: 2001-04-01

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• In this Subject: Pharmacology
• By this author: Tsuchiya H.

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