AbstractThe aim of the following work was to develop the application of an nmr method, using lanthanide ions as probes, to the study of phospholipid vesicular membranes and their interactions with membrane active compounds.
Chapter 1 gives a general introduction to the field of biological and model membranes, nmr methods and the use of lanthanide ions. Chapter 11 illustrates and discusses the 1H, 3 1P and 1 3C-nmr of small phospholipid vesicular membranes and the effect of interactions with lanthanide ions. Chapter 111 shows how 1H-nmr and 3 1P-nmr can be used to monitor ionophore mediated transport of lanthanide ions across sonicated vesicular membranes. The metal ion-ionophore stoichiometries and the activation energies of transport were measured. The transport of the charged ion-ionophore complexes into the vesicles was found to be accompanied by an efflux of protons. These observations are discussed in terms of a carrier mechanism.
Chapter lV describes and discusses experiments to investigate the result of introducing into phosphatidylcholine vesicles physiological concentrations of lipids known to stabilise non-bilayer phases. Rates of transbilayer transport, lipid exchange and vesicle-vesicle fusion and the effects of ca++ on these were measured. The effect of temperature on liposomes composed of phospholipid extracted from Micrococcus CryophiZus and of lipid peroxidation were also examined in relation to changes in lipid organisation.
Chapter V extends the above methods to the study of the mechanism of action of calcium antagonist drugs. At low concentrations the antagonists were found to inhibit ionophore mediated transport of lanthanide ions, but at higher concentrations promotion occurred. A mechanism is proposed in terms of a membrane surface activity of these drugs.
The results show that in general the aim of the project has been justified in that a successful application of the lanthanide-ion-nmr method has been made and useful conclusions reached in each of the areas studied.
|Date of Award||Nov 1982|