title: Lipid-protein interactions and effect of local anesthetics in acetylcholine receptor-rich membranes from Torpedo marmorata electric organ.
abstract: The selectivity of lipid-protein interaction for spin-labeled phospholipids and gangliosides in nicotinic acetylcholine receptor-rich membranes from Torpedo marmorata has been studied by ESR spectroscopy. The association constants of the spin-labeled lipids (relative to phosphatidylcholine) at pH 8.0 are in the order cardiolipin (5.1) approximately equal to stearic acid (4.9) approximately equal to phosphatidylinositol (4.7) > phosphatidylserine (2.7) > phosphatidylglycerol (1.7) > G(D1b) approximately equal to G(M1) approximately equal to G(M2) approximately equal to G(M3) approximately equal to phosphatidylcholine (1.0) > phosphatidylethanolamine (0.5). No selectivity for mono- or disialogangliosides is found over that for phosphatidylcholine. Aminated local anesthetics were found to compete with spin-labeled phosphatidylinositol, but to a much lesser extent with spin-labeled stearic acid, for sites on the intramembranous surface of the protein. The relative association constant of phosphatidylinositol was reduced in the presence of the different local anesthetics to the following extents: tetracaine (55%) > procaine (35%) approximately benzocaine (30%). For stearic acid, only tetracaine gave an appreciable reduction (30%) in association constant. These displacements represent an intrinsic difference in affinity of the local anesthetics for the lipid-protein interface because the membrane partition coefficients are in the order benzocaine >> tetracaine approximately procaine.
authors.affiliation: Abteilung Spektroskopie, Max-Planck-Institut für biophysikalische Chemie, 37077 Göttingen, Germany.
authors.forename: S B
authors.initials: SB
authors.lastname: Mantipragada
authors.forename: L I
authors.initials: LI
authors.lastname: Horváth
authors.forename: H R
authors.initials: HR
authors.lastname: Arias
authors.forename: G
authors.initials: G
authors.lastname: Schwarzmann
authors.forename: K
authors.initials: K
authors.lastname: Sandhoff
authors.forename: F J
authors.initials: FJ
authors.lastname: Barrantes
authors.forename: D
authors.initials: D
authors.lastname: Marsh
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001566:Benzocaine / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D004557:Electric Organ / Q000187:drug effects / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005732:Gangliosides / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000378:metabolism*; D008956:Models, Chemical; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011343:Procaine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013113:Spin Labels; D013229:Stearic Acids / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D013748:Tetracaine / Q000494:pharmacology; D014101:Torpedo
chemical_list: D000779:Anesthetics, Local; D005732:Gangliosides; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D010743:Phospholipids; D011978:Receptors, Nicotinic; D013113:Spin Labels; D013229:Stearic Acids; D013748:Tetracaine; C031183:stearic acid; D011343:Procaine; D001566:Benzocaine