ISSN:
1432-1017
Keywords:
Halothane
;
DPPC
;
DMPC
;
DSC
;
Freeze fracture electron microscopy
;
31P-NMR
;
Model membranes
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Physics
Notes:
Abstract The effect of the volatile anaesthetic halothane on the structure and dynamics of lipid multilayers (dimyristoyl- and dipalmitoylphosphatidylcholine, DM-and DP-PC, aqueous dispersions) was studied using Differential Scanning Calorimetry (DSC), Freeze Fracture Electron Microscopy and solid state phosphorus-31 Nuclear Magnetic Resonance (31P-NMR). The action of the drug depends upon the halothane-to-lipid molar ratio, Ri, and temperature. With DPPC lipids, three main regions can be distinguished: i) 0 〈 Ri 〈 0.7, ii) 0.7 〈 Ri 〈 2 and iii) Ri 〉 2. As Ri increases in the first region, a linear decrease in the main gel-to-fluid phase transition temperature (T c, a broadening in the DSC transition peak and a lowering in the enthalpy variation (ΔH), are observed. A minimum in ΔH is reached at Ri=0.7. In this region, 31P-NMR spectra indicate that the multibilayer structure is maintained. In the second region, T c still decreases with the same slope, but ΔH increases up to a plateau value for Ri=2. In the lipid fluid phase, an isotropic NMR line appears superimposed on the powder pattern that corresponds to a lamellar phase. For Ri 〉 2, T c and ΔH remain almost constant. At values of temperature that are greater than T c a growing isotropic line occurs in 31P-NMR spectra. This means a new supramolecular structure made of lipids and halothane is stabilized. This structure has been characterized as small vesicles of about 400 Å to 600 Å diameter by Freeze Fracture electron microscopy observations. With DMPC and low ratios (Ri 〈 2), DSC and NMR results are similar to those obtained for DPPC. However, the minimum ΔH is reached at Ri=0.2 and the decrease in T c is faster than for DPPC when Ri increases from 0. For Ri 〉 2, while T c and ΔH remain constant as in the case of DPPC, 31P-NMR spectra of DMPC systems show a superimposition of an isotropic line and two powder patterns, which correspond to small tumbling vesicles, a possible hexagonal phase and a lamellar phase respectively. Halothane, thus acts on model membranes in two different steps: at low Ri the bilayer is disturbed but keeps its structure. Whereas for higher drug concentrations, a new organization of lipids seems to be stabilized for T 〉 T c.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00183535
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