title: The Effect of Lidocaine · HCl on the Fluidity of Native and Model Membrane Lipid Bilayers.
abstract: The purpose of this study is to investigated the mechanism of pharmacological action of local anesthetic and provide the basic information about the development of new effective local anesthetics. Fluorescent probe techniques were used to evaluate the effect of lidocaine·HCl on the physical properties (transbilayer asymmetric lateral and rotational mobility, annular lipid fluidity and protein distribution) of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine cerebral cortex, and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from the SPMV. An experimental procedure was used based on selective quenching of 1,3-di(1-pyrenyl)propane (Py-3-Py) and 1,6-diphenyl-1,3,5-hexatriene (DPH) by trinitrophenyl groups, and radiationless energy transfer from the tryptophans of membrane proteins to Py-3-Py. Lidocaine·HCl increased the bulk lateral and rotational mobility of neuronal and model membrane lipid bilayes, and had a greater fluidizing effect on the inner monolayer than the outer monolayer. Lidocaine·HCl increased annular lipid fluidity in SPMV lipid bilayers. It also caused membrane proteins to cluster. The most important finding of this study is that there is far greater increase in annular lipid fluidity than that in lateral and rotational mobilities by lidocaine·HCl. Lidocaine·HCl alters the stereo or dynamics of the proteins in the lipid bilayers by combining with lipids, especially with the annular lipids. In conclusion, the present data suggest that lidocaine, in addition to its direct interaction with proteins, concurrently interacts with membrane lipids, fluidizing the membrane, and thus inducing conformational changes of proteins known to be intimately associated with membrane lipid.
authors.affiliation: Department of Dental Pharmacology and Biophysics, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
authors.forename: Jun-Seop
authors.initials: JS
authors.lastname: Park
authors.forename: Tae-Sang
authors.initials: TS
authors.lastname: Jung
authors.forename: Yang-Ho
authors.initials: YH
authors.lastname: Noh
authors.forename: Woo-Sung
authors.initials: WS
authors.lastname: Kim
authors.forename: Won-Ick
authors.initials: WI
authors.lastname: Park
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: In-Kyo
authors.initials: IK
authors.lastname: Chung
authors.forename: Uy Dong
authors.initials: UD
authors.lastname: Sohn
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Bae
authors.forename: Moon-Kyoung
authors.initials: MK
authors.lastname: Bae
authors.forename: Hye-Ock
authors.initials: HO
authors.lastname: Jang
authors.forename: Il
authors.initials: I
authors.lastname: Yun