title: Spin label study of local anesthetic-lipid membrane interactions. Phase separation of the uncharged form and bilayer micellization by the charged form of tetracaine.
abstract: The interaction between tetracaine and egg phosphatidylcholine (egg PC) multibilayers was examined. ESR spectra of an ester spin label indicate that at low uncharged anesthetic: lipid ratios, membrane organization decreases. At higher ratios, saturation and phase separation occur, as suggested by a second spectral component which appears when the water solubility of tetracaine is reached. However, experiments with the drug in the absence and in the presence of membranes, making use of a phospholipid spin label, suggest that the new phase does not consist of solid tetracaine alone. Location of the new phase in the membrane would require a change in partition coefficient, while its location outside would imply a mechanism whereby the anesthetic would come off the membrane as an aggregate containing spin probe and phospholipid. Charged tetracaine forms micelles which disrupt-unilamellar egg PC vesicles (Fernandez, M.S. (1981) Biochim. Biophys. Acta 646, 27-30). Micellar tetracaine added to bilayers containing a PC spin probe changes the spectrum from one typical of a bilayer into one typical of micelles, indicating the formation of a tetracaine-egg PC mixed micelle. The effect is reversible upon dilution to concentrations below the critical micelle concentration of tetracaine. When membranes are prepared in the presence of a water-soluble spin label, TEMPOcholine, ascorbate destroys the signal of untrapped label; when mixed phospholipid-tetracaine are formed by addition of micellar tetracaine, this leads to a complete loss of the ESR signal. High drug concentrations are often used for anesthesia and could be related to morphological nerve damage caused by large doses of anesthetics.
mesh_terms: D000779:Anesthetics, Local / Q000378:metabolism*; D003497:Cyclic N-Oxides / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D008051:Lipid Bilayers / Q000378:metabolism*; D008823:Micelles; D010713:Phosphatidylcholines / Q000378:metabolism; D013113:Spin Labels; D013748:Tetracaine / Q000378:metabolism*
chemical_list: D000779:Anesthetics, Local; D003497:Cyclic N-Oxides; D008051:Lipid Bilayers; D008823:Micelles; D010713:Phosphatidylcholines; D013113:Spin Labels; D013748:Tetracaine; C017743:tempocholine