KMID : 0811720120160060413
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Korean Journal of Physiology & Pharmacology 2012 Volume.16 No. 6 p.413 ~ p.422
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The Effect of Lidocaine¤ýHCl on the Fluidity of Native and Model Membrane Lipid Bilayers
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Park Jun-Seop
Jung Tae-Sang Noh Yang-Ho Kim Woo-Sung Park Won-Ick Kim Young-Soo Chung In-Kyo Sohn Uy-Dong Bae Soo-Kyung Bae Moon-Kyoung Jang Hye-Ock Yun Il
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Abstract
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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¤ýHCl 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¤ýHCl 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¤ýHCl 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¤ýHCl. Lidocaine¤ýHCl 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.
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KEYWORD
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Annular lipid fluidity, Lidocaine¤ýHCl, Membrane protein clustering, Neuronal and model membranes, Transbilayer lateral and rotational mobility
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